Publications
2025
Ng, Elizabeth S.; Sarila, Gulcan; Li, Jacky Y.; Edirisinghe, Hasindu S.; Saxena, Ritika; Sun, Shicheng; Bruveris, Freya F.; Labonne, Tanya; Sleebs, Nerida; Maytum, Alexander; Yow, Raymond Y.; Inguanti, Chantelle; Motazedian, Ali; Calvanese, Vincenzo; Capellera-Garcia, Sandra; Ma, Feiyang; Nim, Hieu T.; Ramialison, Mirana; Bonifer, Constanze; Mikkola, Hanna K. A.; Stanley, Edouard G.; Elefanty, Andrew G.
Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells Journal Article
In: Nature Biotechnology, vol. 43, no. 8, pp. 1274–1287, 2025, ISSN: 1087-0156, 1546-1696.
@article{ng_long-term_2025,
title = {Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells},
author = {Elizabeth S. Ng and Gulcan Sarila and Jacky Y. Li and Hasindu S. Edirisinghe and Ritika Saxena and Shicheng Sun and Freya F. Bruveris and Tanya Labonne and Nerida Sleebs and Alexander Maytum and Raymond Y. Yow and Chantelle Inguanti and Ali Motazedian and Vincenzo Calvanese and Sandra Capellera-Garcia and Feiyang Ma and Hieu T. Nim and Mirana Ramialison and Constanze Bonifer and Hanna K. A. Mikkola and Edouard G. Stanley and Andrew G. Elefanty},
url = {https://www.nature.com/articles/s41587-024-02360-7},
doi = {10.1038/s41587-024-02360-7},
issn = {1087-0156, 1546-1696},
year = {2025},
date = {2025-08-01},
urldate = {2025-09-18},
journal = {Nature Biotechnology},
volume = {43},
number = {8},
pages = {1274–1287},
abstract = {Abstract
Hematopoietic stem cells (HSCs) derived from human induced pluripotent stem cells (iPS cells) have important biomedical applications. We identified differentiation conditions that generate HSCs defined by robust long-term multilineage engraftment in immune-deficient NOD,B6.
Prkdc
scid
Il2rg
tm1Wjl/SzJ
Kit
W41/W41
mice. We guided differentiating iPS cells, as embryoid bodies in a defined culture medium supplemented with retinyl acetate, through
HOXA
-patterned mesoderm to hemogenic endothelium specified by bone morphogenetic protein 4 and vascular endothelial growth factor (VEGF). Removal of VEGF facilitated an efficient endothelial-to-hematopoietic transition, evidenced by release into the culture medium of CD34
+
blood cells, which were cryopreserved. Intravenous transplantation of two million thawed CD34
+
cells differentiated from four independent iPS cell lines produced multilineage bone marrow engraftment in 25–50% of immune-deficient recipient mice. These functionally defined, multipotent CD34
+
hematopoietic cells, designated iPS cell-derived HSCs (iHSCs), produced levels of engraftment similar to those achieved following umbilical cord blood transplantation. Our study provides a step toward the goal of generating HSCs for clinical translation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hematopoietic stem cells (HSCs) derived from human induced pluripotent stem cells (iPS cells) have important biomedical applications. We identified differentiation conditions that generate HSCs defined by robust long-term multilineage engraftment in immune-deficient NOD,B6.
Prkdc
scid
Il2rg
tm1Wjl/SzJ
Kit
W41/W41
mice. We guided differentiating iPS cells, as embryoid bodies in a defined culture medium supplemented with retinyl acetate, through
HOXA
-patterned mesoderm to hemogenic endothelium specified by bone morphogenetic protein 4 and vascular endothelial growth factor (VEGF). Removal of VEGF facilitated an efficient endothelial-to-hematopoietic transition, evidenced by release into the culture medium of CD34
+
blood cells, which were cryopreserved. Intravenous transplantation of two million thawed CD34
+
cells differentiated from four independent iPS cell lines produced multilineage bone marrow engraftment in 25–50% of immune-deficient recipient mice. These functionally defined, multipotent CD34
+
hematopoietic cells, designated iPS cell-derived HSCs (iHSCs), produced levels of engraftment similar to those achieved following umbilical cord blood transplantation. Our study provides a step toward the goal of generating HSCs for clinical translation.
2024
Yoo, Sang Pil; Yuan, Xuegang; Engstrom, Claire; Chang, Patrick; Li, Suwen; Lathrop, Lindsay; Lagosh, Jessica; Saripalli, Satvik; Azzun, Anthony; Calvanese, Vincenzo; Mikkola, Hanna; Seet, Christopher; Kohn, Donald B.; Crooks, Gay M.
Stage-specific CAR-mediated signaling generates naïve-like, TCR-null CAR T cells from induced pluripotent stem cells Miscellaneous
2024.
@misc{yoo_stage-specific_2024,
title = {Stage-specific CAR-mediated signaling generates naïve-like, TCR-null CAR T cells from induced pluripotent stem cells},
author = {Sang Pil Yoo and Xuegang Yuan and Claire Engstrom and Patrick Chang and Suwen Li and Lindsay Lathrop and Jessica Lagosh and Satvik Saripalli and Anthony Azzun and Vincenzo Calvanese and Hanna Mikkola and Christopher Seet and Donald B. Kohn and Gay M. Crooks},
url = {http://biorxiv.org/lookup/doi/10.1101/2024.11.25.624041},
doi = {10.1101/2024.11.25.624041},
year = {2024},
date = {2024-11-01},
urldate = {2025-09-18},
publisher = {Bioengineering},
abstract = {Abstract
Genetically modified, induced pluripotent stem cells (iPSCs) offer a promising allogeneic source for the generation of functionally enhanced, chimeric antigen receptor (CAR) T cells. However, the signaling of CARs during early T cell development and the removal of the endogenous T cell receptor required to prevent alloreactivity pose significant challenges to the production of mature conventional CAR T cells from iPSCs. Here, we show that TCR-null, CD8αβ CAR T cells can be efficiently generated from iPSCs by engineering stage-specific onset of CAR expression and signaling to both permit conventional T cell development and to induce efficient positive selection. CAR T cells produced using this approach displayed a uniform, naïve T cell phenotype and demonstrated superior antigen-specific cytotoxicity compared to iPSC-derived effector memory CAR T cells. Multimodal sequencing revealed CAR-mediated positive selection induced the persistent upregulation of key transcription factors involved in naïve T cell development. Achieving precise control of CAR expression and signaling in developmentally sensitive T precursors will be critical to realizing the full potential for “off-the-shelf”, iPSC-derived cellular therapies.},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Genetically modified, induced pluripotent stem cells (iPSCs) offer a promising allogeneic source for the generation of functionally enhanced, chimeric antigen receptor (CAR) T cells. However, the signaling of CARs during early T cell development and the removal of the endogenous T cell receptor required to prevent alloreactivity pose significant challenges to the production of mature conventional CAR T cells from iPSCs. Here, we show that TCR-null, CD8αβ CAR T cells can be efficiently generated from iPSCs by engineering stage-specific onset of CAR expression and signaling to both permit conventional T cell development and to induce efficient positive selection. CAR T cells produced using this approach displayed a uniform, naïve T cell phenotype and demonstrated superior antigen-specific cytotoxicity compared to iPSC-derived effector memory CAR T cells. Multimodal sequencing revealed CAR-mediated positive selection induced the persistent upregulation of key transcription factors involved in naïve T cell development. Achieving precise control of CAR expression and signaling in developmentally sensitive T precursors will be critical to realizing the full potential for “off-the-shelf”, iPSC-derived cellular therapies.
Aguadé-Gorgorió, Júlia; Jami-Alahmadi, Yasaman; Calvanese, Vincenzo; Kardouh, Maya; Fares, Iman; Johnson, Haley; Rezek, Valerie; Ma, Feiyang; Magnusson, Mattias; Wang, Yanling; Shin, Juliana E.; Nance, Karina J.; Goodridge, Helen S.; Liebscher, Simone; Schenke-Layland, Katja; Crooks, Gay M.; Wohlschlegel, James A.; Mikkola, Hanna K. A.
MYCT1 controls environmental sensing in human haematopoietic stem cells Journal Article
In: Nature, vol. 630, no. 8016, pp. 412–420, 2024, ISSN: 0028-0836, 1476-4687.
@article{aguade-gorgorio_myct1_2024,
title = {MYCT1 controls environmental sensing in human haematopoietic stem cells},
author = {Júlia Aguadé-Gorgorió and Yasaman Jami-Alahmadi and Vincenzo Calvanese and Maya Kardouh and Iman Fares and Haley Johnson and Valerie Rezek and Feiyang Ma and Mattias Magnusson and Yanling Wang and Juliana E. Shin and Karina J. Nance and Helen S. Goodridge and Simone Liebscher and Katja Schenke-Layland and Gay M. Crooks and James A. Wohlschlegel and Hanna K. A. Mikkola},
url = {https://www.nature.com/articles/s41586-024-07478-x},
doi = {10.1038/s41586-024-07478-x},
issn = {0028-0836, 1476-4687},
year = {2024},
date = {2024-06-01},
urldate = {2025-09-18},
journal = {Nature},
volume = {630},
number = {8016},
pages = {412–420},
abstract = {Abstract
The processes that govern human haematopoietic stem cell (HSC) self-renewal and engraftment are poorly understood and challenging to recapitulate in culture to reliably expand functional HSCs
1–3
. Here we identify MYC target 1 (MYCT1; also known as MTLC) as a crucial human HSC regulator that moderates endocytosis and environmental sensing in HSCs. MYCT1 is selectively expressed in undifferentiated human haematopoietic stem and progenitor cells (HSPCs) and endothelial cells but becomes markedly downregulated during HSC culture. Lentivirus-mediated knockdown of
MYCT1
prevented human fetal liver and cord blood (CB) HSPC expansion and engraftment. By contrast, restoring MYCT1 expression improved the expansion and engraftment of cultured CB HSPCs. Single-cell RNA sequencing of human CB HSPCs in which
MYCT1
was knocked down or overexpressed revealed that MYCT1 governs important regulatory programmes and cellular properties essential for HSC stemness, such as ETS factor expression and low mitochondrial activity. MYCT1 is localized in the endosomal membrane in HSPCs and interacts with vesicle trafficking regulators and signalling machinery. MYCT1 loss in HSPCs led to excessive endocytosis and hyperactive signalling responses, whereas restoring MYCT1 expression balanced culture-induced endocytosis and dysregulated signalling. Moreover, sorting cultured CB HSPCs on the basis of lowest endocytosis rate identified HSPCs with preserved MYCT1 expression and MYCT1-regulated HSC stemness programmes. Our work identifies MYCT1-moderated endocytosis and environmental sensing as essential regulatory mechanisms required to preserve human HSC stemness. Our data also pinpoint silencing of MYCT1 as a cell-culture-induced vulnerability that compromises human HSC expansion.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The processes that govern human haematopoietic stem cell (HSC) self-renewal and engraftment are poorly understood and challenging to recapitulate in culture to reliably expand functional HSCs
1–3
. Here we identify MYC target 1 (MYCT1; also known as MTLC) as a crucial human HSC regulator that moderates endocytosis and environmental sensing in HSCs. MYCT1 is selectively expressed in undifferentiated human haematopoietic stem and progenitor cells (HSPCs) and endothelial cells but becomes markedly downregulated during HSC culture. Lentivirus-mediated knockdown of
MYCT1
prevented human fetal liver and cord blood (CB) HSPC expansion and engraftment. By contrast, restoring MYCT1 expression improved the expansion and engraftment of cultured CB HSPCs. Single-cell RNA sequencing of human CB HSPCs in which
MYCT1
was knocked down or overexpressed revealed that MYCT1 governs important regulatory programmes and cellular properties essential for HSC stemness, such as ETS factor expression and low mitochondrial activity. MYCT1 is localized in the endosomal membrane in HSPCs and interacts with vesicle trafficking regulators and signalling machinery. MYCT1 loss in HSPCs led to excessive endocytosis and hyperactive signalling responses, whereas restoring MYCT1 expression balanced culture-induced endocytosis and dysregulated signalling. Moreover, sorting cultured CB HSPCs on the basis of lowest endocytosis rate identified HSPCs with preserved MYCT1 expression and MYCT1-regulated HSC stemness programmes. Our work identifies MYCT1-moderated endocytosis and environmental sensing as essential regulatory mechanisms required to preserve human HSC stemness. Our data also pinpoint silencing of MYCT1 as a cell-culture-induced vulnerability that compromises human HSC expansion.
Peripolli, Silvia; Meneguello, Leticia; Perrod, Chiara; Singh, Tanya; Patel, Harshil; Rahman, Sazia T.; Kiso, Koshiro; Thorpe, Peter; Calvanese, Vincenzo; Bertoli, Cosetta; Bruin, Robertus A. M. De
Oncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner Journal Article
In: Nature Communications, vol. 15, no. 1, pp. 1579, 2024, ISSN: 2041-1723.
@article{peripolli_oncogenic_2024,
title = {Oncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner},
author = {Silvia Peripolli and Leticia Meneguello and Chiara Perrod and Tanya Singh and Harshil Patel and Sazia T. Rahman and Koshiro Kiso and Peter Thorpe and Vincenzo Calvanese and Cosetta Bertoli and Robertus A. M. De Bruin},
url = {https://www.nature.com/articles/s41467-024-45955-z},
doi = {10.1038/s41467-024-45955-z},
issn = {2041-1723},
year = {2024},
date = {2024-02-01},
urldate = {2025-09-18},
journal = {Nature Communications},
volume = {15},
number = {1},
pages = {1579},
abstract = {Abstract
Oncogene-induced replication stress is a crucial driver of genomic instability and one of the key events contributing to the onset and evolution of cancer. Despite its critical role in cancer, the mechanisms that generate oncogene-induced replication stress remain not fully understood. Here, we report that an oncogenic c-Myc-dependent increase in cohesins on DNA contributes to the induction of replication stress. Accumulation of cohesins on chromatin is not sufficient to cause replication stress, but also requires cohesins to accumulate at specific sites in a CTCF-dependent manner. We propose that the increased accumulation of cohesins at CTCF site interferes with the progression of replication forks, contributing to oncogene-induced replication stress. This is different from, and independent of, previously suggested mechanisms of oncogene-induced replication stress. This, together with the reported protective role of cohesins in preventing replication stress-induced DNA damage, supports a double-edge involvement of cohesins in causing and tolerating oncogene-induced replication stress.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Oncogene-induced replication stress is a crucial driver of genomic instability and one of the key events contributing to the onset and evolution of cancer. Despite its critical role in cancer, the mechanisms that generate oncogene-induced replication stress remain not fully understood. Here, we report that an oncogenic c-Myc-dependent increase in cohesins on DNA contributes to the induction of replication stress. Accumulation of cohesins on chromatin is not sufficient to cause replication stress, but also requires cohesins to accumulate at specific sites in a CTCF-dependent manner. We propose that the increased accumulation of cohesins at CTCF site interferes with the progression of replication forks, contributing to oncogene-induced replication stress. This is different from, and independent of, previously suggested mechanisms of oncogene-induced replication stress. This, together with the reported protective role of cohesins in preventing replication stress-induced DNA damage, supports a double-edge involvement of cohesins in causing and tolerating oncogene-induced replication stress.
2023
Calvanese, Vincenzo; Mikkola, Hanna K. A.
The genesis of human hematopoietic stem cells Journal Article
In: Blood, vol. 142, no. 6, pp. 519–532, 2023, ISSN: 0006-4971, 1528-0020.
@article{calvanese_genesis_2023,
title = {The genesis of human hematopoietic stem cells},
author = {Vincenzo Calvanese and Hanna K. A. Mikkola},
url = {https://ashpublications.org/blood/article/142/6/519/496470/The-genesis-of-human-hematopoietic-stem-cells},
doi = {10.1182/blood.2022017934},
issn = {0006-4971, 1528-0020},
year = {2023},
date = {2023-08-01},
urldate = {2025-09-18},
journal = {Blood},
volume = {142},
number = {6},
pages = {519–532},
abstract = {Abstract
Developmental hematopoiesis consists of multiple, partially overlapping hematopoietic waves that generate the differentiated blood cells required for embryonic development while establishing a pool of undifferentiated hematopoietic stem cells (HSCs) for postnatal life. This multilayered design in which active hematopoiesis migrates through diverse extra and intraembryonic tissues has made it difficult to define a roadmap for generating HSCs vs non–self-renewing progenitors, especially in humans. Recent single-cell studies have helped in identifying the rare human HSCs at stages when functional assays are unsuitable for distinguishing them from progenitors. This approach has made it possible to track the origin of human HSCs to the unique type of arterial endothelium in the aorta-gonad-mesonephros region and document novel benchmarks for HSC migration and maturation in the conceptus. These studies have delivered new insights into the intricate process of HSC generation and provided tools to inform the in vitro efforts to replicate the physiological developmental journey from pluripotent stem cells via distinct mesodermal and endothelial intermediates to HSCs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Developmental hematopoiesis consists of multiple, partially overlapping hematopoietic waves that generate the differentiated blood cells required for embryonic development while establishing a pool of undifferentiated hematopoietic stem cells (HSCs) for postnatal life. This multilayered design in which active hematopoiesis migrates through diverse extra and intraembryonic tissues has made it difficult to define a roadmap for generating HSCs vs non–self-renewing progenitors, especially in humans. Recent single-cell studies have helped in identifying the rare human HSCs at stages when functional assays are unsuitable for distinguishing them from progenitors. This approach has made it possible to track the origin of human HSCs to the unique type of arterial endothelium in the aorta-gonad-mesonephros region and document novel benchmarks for HSC migration and maturation in the conceptus. These studies have delivered new insights into the intricate process of HSC generation and provided tools to inform the in vitro efforts to replicate the physiological developmental journey from pluripotent stem cells via distinct mesodermal and endothelial intermediates to HSCs.
2022
Boutoual, Rachid; Jo, Hyunsun; Heckenbach, Indra; Tiwari, Ritesh; Kasler, Herbert; Lerner, Chad A.; Shah, Samah; Schilling, Birgit; Calvanese, Vincenzo; Rardin, Matthew J.; Scheibye-Knudsen, Morten; Verdin, Eric
A novel splice variant of Elp3/Kat9 regulates mitochondrial tRNA modification and function Journal Article
In: Scientific Reports, vol. 12, no. 1, pp. 14804, 2022, ISSN: 2045-2322.
@article{boutoual_novel_2022,
title = {A novel splice variant of Elp3/Kat9 regulates mitochondrial tRNA modification and function},
author = {Rachid Boutoual and Hyunsun Jo and Indra Heckenbach and Ritesh Tiwari and Herbert Kasler and Chad A. Lerner and Samah Shah and Birgit Schilling and Vincenzo Calvanese and Matthew J. Rardin and Morten Scheibye-Knudsen and Eric Verdin},
url = {https://www.nature.com/articles/s41598-022-18114-x},
doi = {10.1038/s41598-022-18114-x},
issn = {2045-2322},
year = {2022},
date = {2022-08-01},
urldate = {2025-09-18},
journal = {Scientific Reports},
volume = {12},
number = {1},
pages = {14804},
abstract = {Abstract
Post-translational modifications, such as lysine acetylation, regulate the activity of diverse proteins across many cellular compartments. Protein deacetylation in mitochondria is catalyzed by the enzymatic activity of the NAD
+
-dependent deacetylase sirtuin 3 (SIRT3), however it remains unclear whether corresponding mitochondrial acetyltransferases exist. We used a bioinformatics approach to search for mitochondrial proteins with an acetyltransferase catalytic domain, and identified a novel splice variant of ELP3 (mt-ELP3) of the elongator complex, which localizes to the mitochondrial matrix in mammalian cells. Unexpectedly, mt-ELP3 does not mediate mitochondrial protein acetylation but instead induces a post-transcriptional modification of mitochondrial-transfer RNAs (mt-tRNAs). Overexpression of mt-ELP3 leads to the protection of mt-tRNAs against the tRNA-specific RNase angiogenin, increases mitochondrial translation, and furthermore increases expression of OXPHOS complexes. This study thus identifies mt-ELP3 as a non-canonical mt-tRNA modifying enzyme.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Post-translational modifications, such as lysine acetylation, regulate the activity of diverse proteins across many cellular compartments. Protein deacetylation in mitochondria is catalyzed by the enzymatic activity of the NAD
+
-dependent deacetylase sirtuin 3 (SIRT3), however it remains unclear whether corresponding mitochondrial acetyltransferases exist. We used a bioinformatics approach to search for mitochondrial proteins with an acetyltransferase catalytic domain, and identified a novel splice variant of ELP3 (mt-ELP3) of the elongator complex, which localizes to the mitochondrial matrix in mammalian cells. Unexpectedly, mt-ELP3 does not mediate mitochondrial protein acetylation but instead induces a post-transcriptional modification of mitochondrial-transfer RNAs (mt-tRNAs). Overexpression of mt-ELP3 leads to the protection of mt-tRNAs against the tRNA-specific RNase angiogenin, increases mitochondrial translation, and furthermore increases expression of OXPHOS complexes. This study thus identifies mt-ELP3 as a non-canonical mt-tRNA modifying enzyme.
Fares, Iman; Calvanese, Vincenzo; Mikkola, Hanna K. A.
Decoding Human Hematopoietic Stem Cell Self-Renewal Journal Article
In: Current Stem Cell Reports, vol. 8, no. 2, pp. 93–106, 2022, ISSN: 2198-7866.
@article{fares_decoding_2022,
title = {Decoding Human Hematopoietic Stem Cell Self-Renewal},
author = {Iman Fares and Vincenzo Calvanese and Hanna K. A. Mikkola},
url = {https://link.springer.com/10.1007/s40778-022-00209-w},
doi = {10.1007/s40778-022-00209-w},
issn = {2198-7866},
year = {2022},
date = {2022-06-01},
urldate = {2025-09-18},
journal = {Current Stem Cell Reports},
volume = {8},
number = {2},
pages = {93–106},
abstract = {Abstract
Purpose of Review
Hematopoietic stem cells (HSCs) maintain blood and immune cell homeostasis by balancing quiescence, self-renewal, and differentiation. HSCs can be used in lifesaving transplantation treatments to create a healthy hematopoietic system in patients suffering from malignant or inherited blood diseases. However, lack of matching bone marrow donors, and the low quantity of HSCs in a single cord blood graft, are limitations for successful transplantation. The enormous regenerative potential of HSCs has raised the hope that HSC self-renewal could be recapitulated in culture to achieve robust expansion of HSCs for therapeutic use. Yet, when HSCs are cultured ex vivo their function becomes compromised, limiting successful expansion.
Recent Findings
After decades of efforts to expand human HSCs ex vivo that resulted in minimal increase in transplantable units, recent studies have helped define culture conditions that can increase functional HSCs. These studies have provided new insights into how HSC stemness can be controlled from the nucleus by transcriptional, posttranscriptional and epigenetic regulators, or by improving the HSC microenvironment using 3D scaffolds, niche cells, or signaling molecules that mimic specific aspects of human HSC niche. Recent studies have also highlighted the importance of mitigating culture induced cellular stress and balancing mitochondrial, endoplasmic reticulum, and lysosomal functions. These discoveries have provided better markers for functional human HSCs and new insights into how HSC self-renewal and engraftment ability may be controlled ex vivo.
Summary
Uncovering the mechanisms that control the human HSC self-renewal process may help improve the ex vivo expansion of HSCs for clinical purposes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Purpose of Review
Hematopoietic stem cells (HSCs) maintain blood and immune cell homeostasis by balancing quiescence, self-renewal, and differentiation. HSCs can be used in lifesaving transplantation treatments to create a healthy hematopoietic system in patients suffering from malignant or inherited blood diseases. However, lack of matching bone marrow donors, and the low quantity of HSCs in a single cord blood graft, are limitations for successful transplantation. The enormous regenerative potential of HSCs has raised the hope that HSC self-renewal could be recapitulated in culture to achieve robust expansion of HSCs for therapeutic use. Yet, when HSCs are cultured ex vivo their function becomes compromised, limiting successful expansion.
Recent Findings
After decades of efforts to expand human HSCs ex vivo that resulted in minimal increase in transplantable units, recent studies have helped define culture conditions that can increase functional HSCs. These studies have provided new insights into how HSC stemness can be controlled from the nucleus by transcriptional, posttranscriptional and epigenetic regulators, or by improving the HSC microenvironment using 3D scaffolds, niche cells, or signaling molecules that mimic specific aspects of human HSC niche. Recent studies have also highlighted the importance of mitigating culture induced cellular stress and balancing mitochondrial, endoplasmic reticulum, and lysosomal functions. These discoveries have provided better markers for functional human HSCs and new insights into how HSC self-renewal and engraftment ability may be controlled ex vivo.
Summary
Uncovering the mechanisms that control the human HSC self-renewal process may help improve the ex vivo expansion of HSCs for clinical purposes.
Calvanese, Vincenzo; Capellera-Garcia, Sandra; Ma, Feiyang; Fares, Iman; Liebscher, Simone; Ng, Elizabeth S.; Ekstrand, Sophia; Aguadé-Gorgorió, Júlia; Vavilina, Anastasia; Lefaudeux, Diane; Nadel, Brian; Li, Jacky Y.; Wang, Yanling; Lee, Lydia K.; Ardehali, Reza; Iruela-Arispe, M. Luisa; Pellegrini, Matteo; Stanley, Ed G.; Elefanty, Andrew G.; Schenke-Layland, Katja; Mikkola, Hanna K. A.
Mapping human haematopoietic stem cells from haemogenic endothelium to birth Journal Article
In: Nature, vol. 604, no. 7906, pp. 534–540, 2022, ISSN: 0028-0836, 1476-4687.
@article{calvanese_mapping_2022,
title = {Mapping human haematopoietic stem cells from haemogenic endothelium to birth},
author = {Vincenzo Calvanese and Sandra Capellera-Garcia and Feiyang Ma and Iman Fares and Simone Liebscher and Elizabeth S. Ng and Sophia Ekstrand and Júlia Aguadé-Gorgorió and Anastasia Vavilina and Diane Lefaudeux and Brian Nadel and Jacky Y. Li and Yanling Wang and Lydia K. Lee and Reza Ardehali and M. Luisa Iruela-Arispe and Matteo Pellegrini and Ed G. Stanley and Andrew G. Elefanty and Katja Schenke-Layland and Hanna K. A. Mikkola},
url = {https://www.nature.com/articles/s41586-022-04571-x},
doi = {10.1038/s41586-022-04571-x},
issn = {0028-0836, 1476-4687},
year = {2022},
date = {2022-04-01},
urldate = {2025-09-18},
journal = {Nature},
volume = {604},
number = {7906},
pages = {534–540},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Boutoual, Rachid; Jo, Hyunsun; Heckenbach, Indra; Tiwari, Ritesh; Kasler, Herbert; Lerner, Chad A.; Shah, Samah; Schilling, Birgit; Calvanese, Vincenzo; Rardin, Matthew J.; Scheibye-Knudsen, Morten; Verdin, Eric
Human Elp3/Kat9 is a mitochondrial tRNA modifying enzyme Miscellaneous
2022.
@misc{boutoual_human_2022,
title = {Human Elp3/Kat9 is a mitochondrial tRNA modifying enzyme},
author = {Rachid Boutoual and Hyunsun Jo and Indra Heckenbach and Ritesh Tiwari and Herbert Kasler and Chad A. Lerner and Samah Shah and Birgit Schilling and Vincenzo Calvanese and Matthew J. Rardin and Morten Scheibye-Knudsen and Eric Verdin},
url = {http://biorxiv.org/lookup/doi/10.1101/2022.03.24.485634},
doi = {10.1101/2022.03.24.485634},
year = {2022},
date = {2022-03-01},
urldate = {2025-09-18},
publisher = {Molecular Biology},
abstract = {Abstract
Post-translational modifications, such as lysine acetylation, regulate the activity of diverse proteins across many cellular compartments. Protein deacetylation in mitochondria is catalyzed by the enzymatic activity of the NAD+-dependent deacetylase sirtuin 3 (SIRT3), however it remains unclear whether corresponding mitochondrial acetyltransferases exist. We used a bioinformatics approach to search for mitochondrial proteins with an acetyltransferase catalytic domain, and identified a novel splice variant of ELP3 (mt-ELP3) of the elongator complex, which localizes to the mitochondrial matrix in mammalian cells. Unexpectedly, mt-ELP3 does not mediate mitochondrial protein acetylation but instead induces a post-transcriptional modification of mitochondrial-transfer RNAs (mt-tRNAs). Overexpression of mt-ELP3 leads to the protection of mt-tRNAs against the tRNA-specific RNase angiogenin, increases mitochondrial translation, and furthermore increases expression of OXPHOS complexes. This study thus identifies mt-ELP3 as a non-canonical mt-tRNA modifying enzyme.},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Post-translational modifications, such as lysine acetylation, regulate the activity of diverse proteins across many cellular compartments. Protein deacetylation in mitochondria is catalyzed by the enzymatic activity of the NAD+-dependent deacetylase sirtuin 3 (SIRT3), however it remains unclear whether corresponding mitochondrial acetyltransferases exist. We used a bioinformatics approach to search for mitochondrial proteins with an acetyltransferase catalytic domain, and identified a novel splice variant of ELP3 (mt-ELP3) of the elongator complex, which localizes to the mitochondrial matrix in mammalian cells. Unexpectedly, mt-ELP3 does not mediate mitochondrial protein acetylation but instead induces a post-transcriptional modification of mitochondrial-transfer RNAs (mt-tRNAs). Overexpression of mt-ELP3 leads to the protection of mt-tRNAs against the tRNA-specific RNase angiogenin, increases mitochondrial translation, and furthermore increases expression of OXPHOS complexes. This study thus identifies mt-ELP3 as a non-canonical mt-tRNA modifying enzyme.
2019
Calvanese, Vincenzo; Nguyen, Andrew T.; Bolan, Timothy J.; Vavilina, Anastasia; Su, Trent; Lee, Lydia K.; Wang, Yanling; Lay, Fides D.; Magnusson, Mattias; Crooks, Gay M.; Kurdistani, Siavash K.; Mikkola, Hanna K. A.
MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment Journal Article
In: Nature, vol. 576, no. 7786, pp. 281–286, 2019, ISSN: 0028-0836, 1476-4687.
@article{calvanese_mllt3_2019,
title = {MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment},
author = {Vincenzo Calvanese and Andrew T. Nguyen and Timothy J. Bolan and Anastasia Vavilina and Trent Su and Lydia K. Lee and Yanling Wang and Fides D. Lay and Mattias Magnusson and Gay M. Crooks and Siavash K. Kurdistani and Hanna K. A. Mikkola},
url = {https://www.nature.com/articles/s41586-019-1790-2},
doi = {10.1038/s41586-019-1790-2},
issn = {0028-0836, 1476-4687},
year = {2019},
date = {2019-12-01},
urldate = {2025-09-18},
journal = {Nature},
volume = {576},
number = {7786},
pages = {281–286},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2018
Grace, Clea S.; Mikkola, Hanna K. A.; Dou, Diana R.; Calvanese, Vincenzo; Ronn, Roger E.; Purton, Louise E.
In: Experimental Hematology, vol. 65, pp. 1–16, 2018, ISSN: 0301472X.
@article{grace_protagonist_2018,
title = {Protagonist or antagonist? The complex roles of retinoids in the regulation of hematopoietic stem cells and their specification from pluripotent stem cells},
author = {Clea S. Grace and Hanna K. A. Mikkola and Diana R. Dou and Vincenzo Calvanese and Roger E. Ronn and Louise E. Purton},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0301472X18306209},
doi = {10.1016/j.exphem.2018.06.287},
issn = {0301472X},
year = {2018},
date = {2018-09-01},
urldate = {2025-09-18},
journal = {Experimental Hematology},
volume = {65},
pages = {1–16},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2016
Ng, Elizabeth S; Azzola, Lisa; Bruveris, Freya F; Calvanese, Vincenzo; Phipson, Belinda; Vlahos, Katerina; Hirst, Claire; Jokubaitis, Vanta J; Yu, Qing C; Maksimovic, Jovana; Liebscher, Simone; Januar, Vania; Zhang, Zhen; Williams, Brenda; Conscience, Aude; Durnall, Jennifer; Jackson, Steven; Costa, Magdaline; Elliott, David; Haylock, David N; Nilsson, Susan K; Saffery, Richard; Schenke-Layland, Katja; Oshlack, Alicia; Mikkola, Hanna K A; Stanley, Edouard G; Elefanty, Andrew G
Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros Journal Article
In: Nature Biotechnology, vol. 34, no. 11, pp. 1168–1179, 2016, ISSN: 1087-0156, 1546-1696.
@article{ng_differentiation_2016,
title = {Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros},
author = {Elizabeth S Ng and Lisa Azzola and Freya F Bruveris and Vincenzo Calvanese and Belinda Phipson and Katerina Vlahos and Claire Hirst and Vanta J Jokubaitis and Qing C Yu and Jovana Maksimovic and Simone Liebscher and Vania Januar and Zhen Zhang and Brenda Williams and Aude Conscience and Jennifer Durnall and Steven Jackson and Magdaline Costa and David Elliott and David N Haylock and Susan K Nilsson and Richard Saffery and Katja Schenke-Layland and Alicia Oshlack and Hanna K A Mikkola and Edouard G Stanley and Andrew G Elefanty},
url = {https://www.nature.com/articles/nbt.3702},
doi = {10.1038/nbt.3702},
issn = {1087-0156, 1546-1696},
year = {2016},
date = {2016-11-01},
urldate = {2025-09-18},
journal = {Nature Biotechnology},
volume = {34},
number = {11},
pages = {1168–1179},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dou, Diana R.; Calvanese, Vincenzo; Sierra, Maria I.; Nguyen, Andrew T.; Minasian, Arazin; Saarikoski, Pamela; Sasidharan, Rajkumar; Ramirez, Christina M.; Zack, Jerome A.; Crooks, Gay M.; Galic, Zoran; Mikkola, Hanna K. A.
Medial HOXA genes demarcate haematopoietic stem cell fate during human development Journal Article
In: Nature Cell Biology, vol. 18, no. 6, pp. 595–606, 2016, ISSN: 1465-7392, 1476-4679.
@article{dou_medial_2016,
title = {Medial HOXA genes demarcate haematopoietic stem cell fate during human development},
author = {Diana R. Dou and Vincenzo Calvanese and Maria I. Sierra and Andrew T. Nguyen and Arazin Minasian and Pamela Saarikoski and Rajkumar Sasidharan and Christina M. Ramirez and Jerome A. Zack and Gay M. Crooks and Zoran Galic and Hanna K. A. Mikkola},
url = {https://www.nature.com/articles/ncb3354},
doi = {10.1038/ncb3354},
issn = {1465-7392, 1476-4679},
year = {2016},
date = {2016-06-01},
urldate = {2025-09-18},
journal = {Nature Cell Biology},
volume = {18},
number = {6},
pages = {595–606},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Calvanese, Vincenzo; Mikkola, Hanna K. A.
Tracking HSC Origin: From Bench to Placenta Journal Article
In: Developmental Cell, vol. 36, no. 5, pp. 479–480, 2016, ISSN: 15345807.
@article{calvanese_tracking_2016,
title = {Tracking HSC Origin: From Bench to Placenta},
author = {Vincenzo Calvanese and Hanna K. A. Mikkola},
url = {https://linkinghub.elsevier.com/retrieve/pii/S1534580716300776},
doi = {10.1016/j.devcel.2016.02.022},
issn = {15345807},
year = {2016},
date = {2016-03-01},
urldate = {2025-09-18},
journal = {Developmental Cell},
volume = {36},
number = {5},
pages = {479–480},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2015
Chavez, Leonard; Calvanese, Vincenzo; Verdin, Eric
HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells Journal Article
In: PLOS Pathogens, vol. 11, no. 6, pp. e1004955, 2015, ISSN: 1553-7374.
@article{chavez_hiv_2015,
title = {HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells},
author = {Leonard Chavez and Vincenzo Calvanese and Eric Verdin},
editor = {Michael Emerman},
url = {https://dx.plos.org/10.1371/journal.ppat.1004955},
doi = {10.1371/journal.ppat.1004955},
issn = {1553-7374},
year = {2015},
date = {2015-06-01},
urldate = {2025-09-18},
journal = {PLOS Pathogens},
volume = {11},
number = {6},
pages = {e1004955},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aguilera, Óscar; González-Sancho, José Manuel; Zazo, Sandra; Rincón, Raúl; Fernández, Agustín F.; Tapia, Olga; Canals, Francesc; Morte, Beatriz; Calvanese, Vincenzo; Orgaz, José L.; Niell, Núria; Aguilar, Susana; Freije, José M.; Graña, Osvaldo; Pisano, David G.; Borrero, Aurea; Martínez-Useros, Javier; Jiménez, Benilde; Fraga, Mario F.; García-Foncillas, Jesús; López-Otín, Carlos; Lafarga, Miguel; Rojo, Federico; Muñoz, Alberto
Nuclear DICKKOPF-1 as a biomarker of chemoresistance and poor clinical outcome in colorectal cancer Journal Article
In: Oncotarget, vol. 6, no. 8, pp. 5903–5917, 2015, ISSN: 1949-2553.
@article{aguilera_nuclear_2015,
title = {Nuclear DICKKOPF-1 as a biomarker of chemoresistance and poor clinical outcome in colorectal cancer},
author = {Óscar Aguilera and José Manuel González-Sancho and Sandra Zazo and Raúl Rincón and Agustín F. Fernández and Olga Tapia and Francesc Canals and Beatriz Morte and Vincenzo Calvanese and José L. Orgaz and Núria Niell and Susana Aguilar and José M. Freije and Osvaldo Graña and David G. Pisano and Aurea Borrero and Javier Martínez-Useros and Benilde Jiménez and Mario F. Fraga and Jesús García-Foncillas and Carlos López-Otín and Miguel Lafarga and Federico Rojo and Alberto Muñoz},
url = {https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.3464},
doi = {10.18632/oncotarget.3464},
issn = {1949-2553},
year = {2015},
date = {2015-03-01},
urldate = {2025-09-18},
journal = {Oncotarget},
volume = {6},
number = {8},
pages = {5903–5917},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Prashad, Sacha Leandra; Calvanese, Vincenzo; Yao, Catherine Yao; Kaiser, Joshua; Wang, Yanling; Sasidharan, Rajkumar; Crooks, Gay; Magnusson, Mattias; Mikkola, Hanna Katri Annikki
GPI-80 Defines Self-Renewal Ability in Hematopoietic Stem Cells during Human Development Journal Article
In: Cell Stem Cell, vol. 16, no. 1, pp. 80–87, 2015, ISSN: 19345909.
@article{prashad_gpi-80_2015,
title = {GPI-80 Defines Self-Renewal Ability in Hematopoietic Stem Cells during Human Development},
author = {Sacha Leandra Prashad and Vincenzo Calvanese and Catherine Yao Yao and Joshua Kaiser and Yanling Wang and Rajkumar Sasidharan and Gay Crooks and Mattias Magnusson and Hanna Katri Annikki Mikkola},
url = {https://linkinghub.elsevier.com/retrieve/pii/S1934590914005128},
doi = {10.1016/j.stem.2014.10.020},
issn = {19345909},
year = {2015},
date = {2015-01-01},
urldate = {2025-09-18},
journal = {Cell Stem Cell},
volume = {16},
number = {1},
pages = {80–87},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2014
Jacobsen, Stine C.; Gillberg, Linn; Bork-Jensen, Jette; Ribel-Madsen, Rasmus; Lara, Ester; Calvanese, Vincenzo; Ling, Charlotte; Fernandez, Agustin F.; Fraga, Mario F.; Poulsen, Pernille; Brøns, Charlotte; Vaag, Allan
Young men with low birthweight exhibit decreased plasticity of genome-wide muscle DNA methylation by high-fat overfeeding Journal Article
In: Diabetologia, vol. 57, no. 6, pp. 1154–1158, 2014, ISSN: 0012-186X, 1432-0428.
@article{jacobsen_young_2014,
title = {Young men with low birthweight exhibit decreased plasticity of genome-wide muscle DNA methylation by high-fat overfeeding},
author = {Stine C. Jacobsen and Linn Gillberg and Jette Bork-Jensen and Rasmus Ribel-Madsen and Ester Lara and Vincenzo Calvanese and Charlotte Ling and Agustin F. Fernandez and Mario F. Fraga and Pernille Poulsen and Charlotte Brøns and Allan Vaag},
url = {http://link.springer.com/10.1007/s00125-014-3198-8},
doi = {10.1007/s00125-014-3198-8},
issn = {0012-186X, 1432-0428},
year = {2014},
date = {2014-06-01},
urldate = {2025-09-18},
journal = {Diabetologia},
volume = {57},
number = {6},
pages = {1154–1158},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Calvanese, V.; Lee, L. K.; Mikkola, H. K. A.
Sex hormone drives blood stem cell reproduction Journal Article
In: The EMBO Journal, vol. 33, no. 6, pp. 534–535, 2014, ISSN: 0261-4189, 1460-2075.
@article{calvanese_sex_2014,
title = {Sex hormone drives blood stem cell reproduction},
author = {V. Calvanese and L. K. Lee and H. K. A. Mikkola},
url = {https://www.embopress.org/doi/full/10.1002/embj.201487976},
doi = {10.1002/embj.201487976},
issn = {0261-4189, 1460-2075},
year = {2014},
date = {2014-03-01},
urldate = {2025-09-18},
journal = {The EMBO Journal},
volume = {33},
number = {6},
pages = {534–535},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2013
Calvanese, Vincenzo; Chavez, Leonard; Laurent, Timothy; Ding, Sheng; Verdin, Eric
Dual-color HIV reporters trace a population of latently infected cells and enable their purification Journal Article
In: Virology, vol. 446, no. 1-2, pp. 283–292, 2013, ISSN: 00426822.
@article{calvanese_dual-color_2013,
title = {Dual-color HIV reporters trace a population of latently infected cells and enable their purification},
author = {Vincenzo Calvanese and Leonard Chavez and Timothy Laurent and Sheng Ding and Eric Verdin},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0042682213004571},
doi = {10.1016/j.virol.2013.07.037},
issn = {00426822},
year = {2013},
date = {2013-11-01},
urldate = {2025-09-18},
journal = {Virology},
volume = {446},
number = {1-2},
pages = {283–292},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Rad, Roland; Cadiñanos, Juan; Rad, Lena; Varela, Ignacio; Strong, Alexander; Kriegl, Lydia; Constantino-Casas, Fernando; Eser, Stefan; Hieber, Maren; Seidler, Barbara; Price, Stacey; Fraga, Mario F.; Calvanese, Vincenzo; Hoffman, Gary; Ponstingl, Hannes; Schneider, Günter; Yusa, Kosuke; Grove, Carolyn; Schmid, Roland M.; Wang, Wei; Vassiliou, George; Kirchner, Thomas; McDermott, Ultan; Liu, Pentao; Saur, Dieter; Bradley, Allan
A Genetic Progression Model of BrafV600E-Induced Intestinal Tumorigenesis Reveals Targets for Therapeutic Intervention Journal Article
In: Cancer Cell, vol. 24, no. 1, pp. 15–29, 2013, ISSN: 15356108.
@article{rad_genetic_2013,
title = {A Genetic Progression Model of BrafV600E-Induced Intestinal Tumorigenesis Reveals Targets for Therapeutic Intervention},
author = {Roland Rad and Juan Cadiñanos and Lena Rad and Ignacio Varela and Alexander Strong and Lydia Kriegl and Fernando Constantino-Casas and Stefan Eser and Maren Hieber and Barbara Seidler and Stacey Price and Mario F. Fraga and Vincenzo Calvanese and Gary Hoffman and Hannes Ponstingl and Günter Schneider and Kosuke Yusa and Carolyn Grove and Roland M. Schmid and Wei Wang and George Vassiliou and Thomas Kirchner and Ultan McDermott and Pentao Liu and Dieter Saur and Allan Bradley},
url = {https://linkinghub.elsevier.com/retrieve/pii/S1535610813002390},
doi = {10.1016/j.ccr.2013.05.014},
issn = {15356108},
year = {2013},
date = {2013-07-01},
urldate = {2025-09-18},
journal = {Cancer Cell},
volume = {24},
number = {1},
pages = {15–29},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Shirakawa, Kotaro; Chavez, Leonard; Hakre, Shweta; Calvanese, Vincenzo; Verdin, Eric
Reactivation of latent HIV by histone deacetylase inhibitors Journal Article
In: Trends in Microbiology, vol. 21, no. 6, pp. 277–285, 2013, ISSN: 0966842X.
@article{shirakawa_reactivation_2013,
title = {Reactivation of latent HIV by histone deacetylase inhibitors},
author = {Kotaro Shirakawa and Leonard Chavez and Shweta Hakre and Vincenzo Calvanese and Eric Verdin},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0966842X13000358},
doi = {10.1016/j.tim.2013.02.005},
issn = {0966842X},
year = {2013},
date = {2013-06-01},
urldate = {2025-09-18},
journal = {Trends in Microbiology},
volume = {21},
number = {6},
pages = {277–285},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Boehm, Daniela; Calvanese, Vincenzo; Dar, Roy D.; Xing, Sifei; Schroeder, Sebastian; Martins, Laura; Aull, Katherine; Li, Pao-Chen; Planelles, Vicente; Bradner, James E.; Zhou, Ming-Ming; Siliciano, Robert F.; Weinberger, Leor; Verdin, Eric; Ott, Melanie
BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism Journal Article
In: Cell Cycle, vol. 12, no. 3, pp. 452–462, 2013, ISSN: 1538-4101, 1551-4005.
@article{boehm_bet_2013,
title = {BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism},
author = {Daniela Boehm and Vincenzo Calvanese and Roy D. Dar and Sifei Xing and Sebastian Schroeder and Laura Martins and Katherine Aull and Pao-Chen Li and Vicente Planelles and James E. Bradner and Ming-Ming Zhou and Robert F. Siliciano and Leor Weinberger and Eric Verdin and Melanie Ott},
url = {http://www.tandfonline.com/doi/abs/10.4161/cc.23309},
doi = {10.4161/cc.23309},
issn = {1538-4101, 1551-4005},
year = {2013},
date = {2013-02-01},
urldate = {2025-09-18},
journal = {Cell Cycle},
volume = {12},
number = {3},
pages = {452–462},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2012
Jacobsen, S. C.; Brøns, C.; Bork-Jensen, J.; Ribel-Madsen, R.; Yang, B.; Lara, E.; Hall, E.; Calvanese, V.; Nilsson, E.; Jørgensen, S. W.; Mandrup, S.; Ling, C.; Fernandez, A. F.; Fraga, M. F.; Poulsen, P.; Vaag, A.
Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men Journal Article
In: Diabetologia, vol. 55, no. 12, pp. 3341–3349, 2012, ISSN: 0012-186X, 1432-0428.
@article{jacobsen_effects_2012,
title = {Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men},
author = {S. C. Jacobsen and C. Brøns and J. Bork-Jensen and R. Ribel-Madsen and B. Yang and E. Lara and E. Hall and V. Calvanese and E. Nilsson and S. W. Jørgensen and S. Mandrup and C. Ling and A. F. Fernandez and M. F. Fraga and P. Poulsen and A. Vaag},
url = {http://link.springer.com/10.1007/s00125-012-2717-8},
doi = {10.1007/s00125-012-2717-8},
issn = {0012-186X, 1432-0428},
year = {2012},
date = {2012-12-01},
urldate = {2025-09-18},
journal = {Diabetologia},
volume = {55},
number = {12},
pages = {3341–3349},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ribel-Madsen, Rasmus; Fraga, Mario F.; Jacobsen, Stine; Bork-Jensen, Jette; Lara, Ester; Calvanese, Vincenzo; Fernandez, Agustin F.; Friedrichsen, Martin; Vind, Birgitte F.; Højlund, Kurt; Beck-Nielsen, Henning; Esteller, Manel; Vaag, Allan; Poulsen, Pernille
Genome-Wide Analysis of DNA Methylation Differences in Muscle and Fat from Monozygotic Twins Discordant for Type 2 Diabetes Journal Article
In: PLoS ONE, vol. 7, no. 12, pp. e51302, 2012, ISSN: 1932-6203.
@article{ribel-madsen_genome-wide_2012,
title = {Genome-Wide Analysis of DNA Methylation Differences in Muscle and Fat from Monozygotic Twins Discordant for Type 2 Diabetes},
author = {Rasmus Ribel-Madsen and Mario F. Fraga and Stine Jacobsen and Jette Bork-Jensen and Ester Lara and Vincenzo Calvanese and Agustin F. Fernandez and Martin Friedrichsen and Birgitte F. Vind and Kurt Højlund and Henning Beck-Nielsen and Manel Esteller and Allan Vaag and Pernille Poulsen},
editor = {Ingrid A. Dahlman},
url = {https://dx.plos.org/10.1371/journal.pone.0051302},
doi = {10.1371/journal.pone.0051302},
issn = {1932-6203},
year = {2012},
date = {2012-12-01},
urldate = {2025-09-18},
journal = {PLoS ONE},
volume = {7},
number = {12},
pages = {e51302},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Huidobro, Covadonga; Urdinguio, Rocío G.; Rodríguez, Ramón María; Mangas, Cristina; Calvanese, Vincenzo; Martínez-Camblor, Pablo; Ferrero, Cecilia; Parra-Blanco, Adolfo; Rodrigo, Luis; Obaya, Álvaro J.; Suárez-Fernández, Laura; Astudillo, Aurora; Hernando, Henar; Ballestar, Esteban; Fernández, Agustín F.; Fraga, Mario F.
A DNA methylation signature associated with aberrant promoter DNA hypermethylation of DNMT3B in human colorectal cancer Journal Article
In: European Journal of Cancer, vol. 48, no. 14, pp. 2270–2281, 2012, ISSN: 09598049.
@article{huidobro_dna_2012,
title = {A DNA methylation signature associated with aberrant promoter DNA hypermethylation of DNMT3B in human colorectal cancer},
author = {Covadonga Huidobro and Rocío G. Urdinguio and Ramón María Rodríguez and Cristina Mangas and Vincenzo Calvanese and Pablo Martínez-Camblor and Cecilia Ferrero and Adolfo Parra-Blanco and Luis Rodrigo and Álvaro J. Obaya and Laura Suárez-Fernández and Aurora Astudillo and Henar Hernando and Esteban Ballestar and Agustín F. Fernández and Mario F. Fraga},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0959804911010689},
doi = {10.1016/j.ejca.2011.12.019},
issn = {09598049},
year = {2012},
date = {2012-09-01},
urldate = {2025-09-18},
journal = {European Journal of Cancer},
volume = {48},
number = {14},
pages = {2270–2281},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cortés, Isabel; Sánchez-Ruíz, Jesús; Zuluaga, Susana; Calvanese, Vincenzo; Marqués, Miriam; Hernández, Carmen; Rivera, Teresa; Kremer, Leonor; González-García, Ana; Carrera, Ana C.
p85β phosphoinositide 3-kinase subunit regulates tumor progression Journal Article
In: Proceedings of the National Academy of Sciences, vol. 109, no. 28, pp. 11318–11323, 2012, ISSN: 0027-8424, 1091-6490.
@article{cortes_p85_2012,
title = {p85β phosphoinositide 3-kinase subunit regulates tumor progression},
author = {Isabel Cortés and Jesús Sánchez-Ruíz and Susana Zuluaga and Vincenzo Calvanese and Miriam Marqués and Carmen Hernández and Teresa Rivera and Leonor Kremer and Ana González-García and Ana C. Carrera},
url = {https://pnas.org/doi/full/10.1073/pnas.1118138109},
doi = {10.1073/pnas.1118138109},
issn = {0027-8424, 1091-6490},
year = {2012},
date = {2012-07-01},
urldate = {2025-09-18},
journal = {Proceedings of the National Academy of Sciences},
volume = {109},
number = {28},
pages = {11318–11323},
abstract = {PIK3R2
encodes a ubiquitous regulatory subunit (p85β) of PI3K, an enzyme that generates 3-polyphosphoinositides at the plasma membrane. PI3K activation triggers cell survival and migration. We found that p85β expression is elevated in breast and colon carcinomas and that its increased expression correlates with PI3K pathway activation and tumor progression. p85β expression induced moderate PIP
3
generation at the cell membrane and enhanced cell invasion. In accordance, genetic alteration of
pik3r2
expression levels modulated tumor progression in vivo. Increased p85β expression thus represents a cellular strategy in cancer progression.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
encodes a ubiquitous regulatory subunit (p85β) of PI3K, an enzyme that generates 3-polyphosphoinositides at the plasma membrane. PI3K activation triggers cell survival and migration. We found that p85β expression is elevated in breast and colon carcinomas and that its increased expression correlates with PI3K pathway activation and tumor progression. p85β expression induced moderate PIP
3
generation at the cell membrane and enhanced cell invasion. In accordance, genetic alteration of
pik3r2
expression levels modulated tumor progression in vivo. Increased p85β expression thus represents a cellular strategy in cancer progression.
Calvanese, Vincenzo; Fernández, Agustín F.; Urdinguio, Rocío G.; Suárez-Alvarez, Beatriz; Mangas, Cristina; Pérez-García, Vicente; Bueno, Clara; Montes, Rosa; Ramos-Mejía, Verónica; Martínez-Camblor, Pablo; Ferrero, Cecilia; Assenov, Yassen; Bock, Christoph; Menendez, Pablo; Carrera, Ana Clara; Lopez-Larrea, Carlos; Fraga, Mario F.
A promoter DNA demethylation landscape of human hematopoietic differentiation Journal Article
In: Nucleic Acids Research, vol. 40, no. 1, pp. 116–131, 2012, ISSN: 1362-4962, 0305-1048.
@article{calvanese_promoter_2012,
title = {A promoter DNA demethylation landscape of human hematopoietic differentiation},
author = {Vincenzo Calvanese and Agustín F. Fernández and Rocío G. Urdinguio and Beatriz Suárez-Alvarez and Cristina Mangas and Vicente Pérez-García and Clara Bueno and Rosa Montes and Verónica Ramos-Mejía and Pablo Martínez-Camblor and Cecilia Ferrero and Yassen Assenov and Christoph Bock and Pablo Menendez and Ana Clara Carrera and Carlos Lopez-Larrea and Mario F. Fraga},
url = {https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkr685},
doi = {10.1093/nar/gkr685},
issn = {1362-4962, 0305-1048},
year = {2012},
date = {2012-01-01},
urldate = {2025-09-18},
journal = {Nucleic Acids Research},
volume = {40},
number = {1},
pages = {116–131},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Calvanese, Vincenzo; Lara, Ester; Fraga, Mario F.
Epigenetic Code and Self-Identity Book Section
In: López-Larrea, Carlos (Ed.): Self and Nonself, vol. 738, pp. 236–255, Springer US, New York, NY, 2012, ISBN: 978-1-4614-1679-1 978-1-4614-1680-7, (Series Title: Advances in Experimental Medicine and Biology).
@incollection{lopez-larrea_epigenetic_2012,
title = {Epigenetic Code and Self-Identity},
author = {Vincenzo Calvanese and Ester Lara and Mario F. Fraga},
editor = {Carlos López-Larrea},
url = {http://link.springer.com/10.1007/978-1-4614-1680-7_14},
doi = {10.1007/978-1-4614-1680-7_14},
isbn = {978-1-4614-1679-1 978-1-4614-1680-7},
year = {2012},
date = {2012-01-01},
urldate = {2025-09-18},
booktitle = {Self and Nonself},
volume = {738},
pages = {236–255},
publisher = {Springer US},
address = {New York, NY},
note = {Series Title: Advances in Experimental Medicine and Biology},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
Calvanese, Vincenzo; Fraga, Mario F.
Epigenetics of Embryonic Stem Cells Book Section
In: López-Larrea, Carlos; López-Vázquez, Antonio; Suárez-Álvarez, Beatriz (Ed.): Stem Cell Transplantation, vol. 741, pp. 231–253, Springer US, New York, NY, 2012, ISBN: 978-1-4614-2097-2 978-1-4614-2098-9, (Series Title: Advances in Experimental Medicine and Biology).
@incollection{lopez-larrea_epigenetics_2012,
title = {Epigenetics of Embryonic Stem Cells},
author = {Vincenzo Calvanese and Mario F. Fraga},
editor = {Carlos López-Larrea and Antonio López-Vázquez and Beatriz Suárez-Álvarez},
url = {http://link.springer.com/10.1007/978-1-4614-2098-9_16},
doi = {10.1007/978-1-4614-2098-9_16},
isbn = {978-1-4614-2097-2 978-1-4614-2098-9},
year = {2012},
date = {2012-01-01},
urldate = {2025-09-18},
booktitle = {Stem Cell Transplantation},
volume = {741},
pages = {231–253},
publisher = {Springer US},
address = {New York, NY},
note = {Series Title: Advances in Experimental Medicine and Biology},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
2011
Calvanese, Vincenzo; Fraga, Mario F.
SirT1 brings stemness closer to cancer and aging Journal Article
In: Aging, vol. 3, no. 2, pp. 162–167, 2011, ISSN: 1945-4589.
@article{calvanese_sirt1_2011,
title = {SirT1 brings stemness closer to cancer and aging},
author = {Vincenzo Calvanese and Mario F. Fraga},
url = {https://www.aging-us.com/lookup/doi/10.18632/aging.100272},
doi = {10.18632/aging.100272},
issn = {1945-4589},
year = {2011},
date = {2011-02-01},
urldate = {2025-09-18},
journal = {Aging},
volume = {3},
number = {2},
pages = {162–167},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lara, Ester; Calvanese, Vincenzo; Fernandez, Agustin F.; Fraga, Mario F.
Techniques to Study DNA Methylation and Histone Modification Book Section
In: Roach, Helmtrud I.; Bronner, Felix; Oreffo, Richard O. C. (Ed.): Epigenetic Aspects of Chronic Diseases, pp. 21–39, Springer London, London, 2011, ISBN: 978-1-84882-643-4 978-1-84882-644-1.
@incollection{roach_techniques_2011,
title = {Techniques to Study DNA Methylation and Histone Modification},
author = {Ester Lara and Vincenzo Calvanese and Agustin F. Fernandez and Mario F. Fraga},
editor = {Helmtrud I. Roach and Felix Bronner and Richard O. C. Oreffo},
url = {http://link.springer.com/10.1007/978-1-84882-644-1_2},
doi = {10.1007/978-1-84882-644-1_2},
isbn = {978-1-84882-643-4 978-1-84882-644-1},
year = {2011},
date = {2011-01-01},
urldate = {2025-09-18},
booktitle = {Epigenetic Aspects of Chronic Diseases},
pages = {21–39},
publisher = {Springer London},
address = {London},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
2010
Fernández-Morera, J. L.; Calvanese, V.; Rodríguez-Rodero, S.; Menéndez-Torre, E.; Fraga, M. F.
Epigenetic regulation of the immune system in health and disease Journal Article
In: Tissue Antigens, vol. 76, no. 6, pp. 431–439, 2010, ISSN: 00012815.
@article{fernandez-morera_epigenetic_2010,
title = {Epigenetic regulation of the immune system in health and disease},
author = {J. L. Fernández-Morera and V. Calvanese and S. Rodríguez-Rodero and E. Menéndez-Torre and M. F. Fraga},
url = {https://onlinelibrary.wiley.com/doi/10.1111/j.1399-0039.2010.01587.x},
doi = {10.1111/j.1399-0039.2010.01587.x},
issn = {00012815},
year = {2010},
date = {2010-12-01},
urldate = {2025-09-18},
journal = {Tissue Antigens},
volume = {76},
number = {6},
pages = {431–439},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lara, Ester; Calvanese, Vincenzo; Huidobro, Covadonga; Fernández, Agustin F; Moncada-Pazos, Ángela; Obaya, Álvaro J; Aguilera, Oscar; González-Sancho, José Manuel; Sánchez, Laura; Astudillo, Aurora; Muñoz, Alberto; López-Otín, Carlos; Esteller, Manel; Fraga, Mario F
Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer Journal Article
In: Molecular Cancer, vol. 9, no. 1, pp. 170, 2010, ISSN: 1476-4598.
@article{lara_epigenetic_2010,
title = {Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer},
author = {Ester Lara and Vincenzo Calvanese and Covadonga Huidobro and Agustin F Fernández and Ángela Moncada-Pazos and Álvaro J Obaya and Oscar Aguilera and José Manuel González-Sancho and Laura Sánchez and Aurora Astudillo and Alberto Muñoz and Carlos López-Otín and Manel Esteller and Mario F Fraga},
url = {https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-9-170},
doi = {10.1186/1476-4598-9-170},
issn = {1476-4598},
year = {2010},
date = {2010-12-01},
urldate = {2025-09-18},
journal = {Molecular Cancer},
volume = {9},
number = {1},
pages = {170},
abstract = {Abstract
Background
Wnt factors control cell differentiation through semi-independent molecular cascades known as the β-catenin-dependent (canonical) and -independent (non-canonical) Wnt signalling pathways. Genetic and epigenetic alteration of components of the canonical Wnt signalling pathway is one of the primary mechanisms underlying colon cancer. Despite increasing evidence of the role of the non-canonical pathways in tumourigenesis, however, the underlying molecular mechanisms are poorly understood.
Results
Here we report that the receptor tyrosine kinase-like orphan receptor 2 (ROR2), a transmembrane receptor for Wnt factors that activates non-canonical pathways, is frequently repressed by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumours. By restoring ROR2 activity in colon cancer cells harbouring
ROR2
promoter hypermethylation, we show that the role of ROR2 in colon cancer cells is mediated, at least in part, by canonical Wnt and that its epigenetic-dependent loss can be pro-tumourigenic.
Conclusions
Our data show the importance of epigenetic alterations of ROR2 in colon cancer, highlighting the close interconnection between canonical and non-canonical Wnt signalling pathways in this type of tumour.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Wnt factors control cell differentiation through semi-independent molecular cascades known as the β-catenin-dependent (canonical) and -independent (non-canonical) Wnt signalling pathways. Genetic and epigenetic alteration of components of the canonical Wnt signalling pathway is one of the primary mechanisms underlying colon cancer. Despite increasing evidence of the role of the non-canonical pathways in tumourigenesis, however, the underlying molecular mechanisms are poorly understood.
Results
Here we report that the receptor tyrosine kinase-like orphan receptor 2 (ROR2), a transmembrane receptor for Wnt factors that activates non-canonical pathways, is frequently repressed by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumours. By restoring ROR2 activity in colon cancer cells harbouring
ROR2
promoter hypermethylation, we show that the role of ROR2 in colon cancer cells is mediated, at least in part, by canonical Wnt and that its epigenetic-dependent loss can be pro-tumourigenic.
Conclusions
Our data show the importance of epigenetic alterations of ROR2 in colon cancer, highlighting the close interconnection between canonical and non-canonical Wnt signalling pathways in this type of tumour.
Calvanese, Vincenzo; Lara, Ester; Suárez-Álvarez, Beatriz; Dawud, Raed Abu; Vázquez-Chantada, Mercedes; Martínez-Chantar, Maria Luz; Embade, Nieves; López-Nieva, Pilar; Horrillo, Angelica; Hmadcha, Abdelkrim; Soria, Bernat; Piazzolla, Daniela; Herranz, Daniel; Serrano, Manuel; Mato, Jose María; Andrews, Peter W.; López-Larrea, Carlos; Esteller, Manel; Fraga, Mario F.
Sirtuin 1 regulation of developmental genes during differentiation of stem cells Journal Article
In: Proceedings of the National Academy of Sciences, vol. 107, no. 31, pp. 13736–13741, 2010, ISSN: 0027-8424, 1091-6490.
@article{calvanese_sirtuin_2010,
title = {Sirtuin 1 regulation of developmental genes during differentiation of stem cells},
author = {Vincenzo Calvanese and Ester Lara and Beatriz Suárez-Álvarez and Raed Abu Dawud and Mercedes Vázquez-Chantada and Maria Luz Martínez-Chantar and Nieves Embade and Pilar López-Nieva and Angelica Horrillo and Abdelkrim Hmadcha and Bernat Soria and Daniela Piazzolla and Daniel Herranz and Manuel Serrano and Jose María Mato and Peter W. Andrews and Carlos López-Larrea and Manel Esteller and Mario F. Fraga},
url = {https://pnas.org/doi/full/10.1073/pnas.1001399107},
doi = {10.1073/pnas.1001399107},
issn = {0027-8424, 1091-6490},
year = {2010},
date = {2010-08-01},
urldate = {2025-09-18},
journal = {Proceedings of the National Academy of Sciences},
volume = {107},
number = {31},
pages = {13736–13741},
abstract = {The longevity-promoting NAD
+
–dependent class III histone deacetylase Sirtuin 1 (SIRT1) is involved in stem cell function by controlling cell fate decision and/or by regulating the p53-dependent expression of NANOG. We show that SIRT1 is down-regulated precisely during human embryonic stem cell differentiation at both mRNA and protein levels and that the decrease in Sirt1 mRNA is mediated by a molecular pathway that involves the RNA-binding protein HuR and the arginine methyltransferase coactivator-associated arginine methyltransferase 1 (CARM1). SIRT1 down-regulation leads to reactivation of key developmental genes such as the neuroretinal morphogenesis effectors DLL4, TBX3, and PAX6, which are epigenetically repressed by this histone deacetylase in pluripotent human embryonic stem cells. Our results indicate that SIRT1 is regulated during stem cell differentiation in the context of a yet-unknown epigenetic pathway that controls specific developmental genes in embryonic stem cells.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
+
–dependent class III histone deacetylase Sirtuin 1 (SIRT1) is involved in stem cell function by controlling cell fate decision and/or by regulating the p53-dependent expression of NANOG. We show that SIRT1 is down-regulated precisely during human embryonic stem cell differentiation at both mRNA and protein levels and that the decrease in Sirt1 mRNA is mediated by a molecular pathway that involves the RNA-binding protein HuR and the arginine methyltransferase coactivator-associated arginine methyltransferase 1 (CARM1). SIRT1 down-regulation leads to reactivation of key developmental genes such as the neuroretinal morphogenesis effectors DLL4, TBX3, and PAX6, which are epigenetically repressed by this histone deacetylase in pluripotent human embryonic stem cells. Our results indicate that SIRT1 is regulated during stem cell differentiation in the context of a yet-unknown epigenetic pathway that controls specific developmental genes in embryonic stem cells.
Suárez-Álvarez, Beatriz; Rodriguez, Ramón M.; Calvanese, Vincenzo; Blanco-Gelaz, Miguel A.; Suhr, Steve T.; Ortega, Francisco; Otero, Jesus; Cibelli, Jose B.; Moore, Harry; Fraga, Mario F.; López-Larrea, Carlos
Epigenetic Mechanisms Regulate MHC and Antigen Processing Molecules in Human Embryonic and Induced Pluripotent Stem Cells Journal Article
In: PLoS ONE, vol. 5, no. 4, pp. e10192, 2010, ISSN: 1932-6203.
@article{suarez-alvarez_epigenetic_2010,
title = {Epigenetic Mechanisms Regulate MHC and Antigen Processing Molecules in Human Embryonic and Induced Pluripotent Stem Cells},
author = {Beatriz Suárez-Álvarez and Ramón M. Rodriguez and Vincenzo Calvanese and Miguel A. Blanco-Gelaz and Steve T. Suhr and Francisco Ortega and Jesus Otero and Jose B. Cibelli and Harry Moore and Mario F. Fraga and Carlos López-Larrea},
editor = {Joanna Mary Bridger},
url = {https://dx.plos.org/10.1371/journal.pone.0010192},
doi = {10.1371/journal.pone.0010192},
issn = {1932-6203},
year = {2010},
date = {2010-04-01},
urldate = {2025-09-18},
journal = {PLoS ONE},
volume = {5},
number = {4},
pages = {e10192},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lara*, Ester; Calvanese*, Vincenzo; Fraga, Mario F.
Epigenetic Drift and Aging Book Section
In: Tollefsbol, Trygve O. (Ed.): Epigenetics of Aging, pp. 257–273, Springer New York, New York, NY, 2010, ISBN: 978-1-4419-0638-0 978-1-4419-0639-7.
@incollection{tollefsbol_epigenetic_2010,
title = {Epigenetic Drift and Aging},
author = {Ester Lara* and Vincenzo Calvanese* and Mario F. Fraga},
editor = {Trygve O. Tollefsbol},
url = {http://link.springer.com/10.1007/978-1-4419-0639-7_14},
doi = {10.1007/978-1-4419-0639-7_14},
isbn = {978-1-4419-0638-0 978-1-4419-0639-7},
year = {2010},
date = {2010-01-01},
urldate = {2025-09-18},
booktitle = {Epigenetics of Aging},
pages = {257–273},
publisher = {Springer New York},
address = {New York, NY},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
2009
Calvanese, Vincenzo; Lara, Ester; Kahn, Arnold; Fraga, Mario F.
The role of epigenetics in aging and age-related diseases Journal Article
In: Ageing Research Reviews, vol. 8, no. 4, pp. 268–276, 2009, ISSN: 15681637.
@article{calvanese_role_2009,
title = {The role of epigenetics in aging and age-related diseases},
author = {Vincenzo Calvanese and Ester Lara and Arnold Kahn and Mario F. Fraga},
url = {https://linkinghub.elsevier.com/retrieve/pii/S1568163709000191},
doi = {10.1016/j.arr.2009.03.004},
issn = {15681637},
year = {2009},
date = {2009-10-01},
urldate = {2025-09-18},
journal = {Ageing Research Reviews},
volume = {8},
number = {4},
pages = {268–276},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Martín-Subero, José I.; Kreuz, Markus; Bibikova, Marina; Bentink, Stefan; Ammerpohl, Ole; Wickham-Garcia, Eliza; Rosolowski, Maciej; Richter, Julia; Lopez-Serra, Lidia; Ballestar, Esteban; Berger, Hilmar; Agirre, Xabier; Bernd, Heinz-Wolfram; Calvanese, Vincenzo; Cogliatti, Sergio B.; Drexler, Hans G.; Fan, Jian-Bing; Fraga, Mario F.; Hansmann, Martin L.; Hummel, Michael; Klapper, Wolfram; Korn, Bernhard; Küppers, Ralf; MacLeod, Roderick A. F.; Möller, Peter; Ott, German; Pott, Christiane; Prosper, Felipe; Rosenwald, Andreas; Schwaenen, Carsten; Schübeler, Dirk; Seifert, Marc; Stürzenhofecker, Benjamin; Weber, Michael; Wessendorf, Swen; Loeffler, Markus; Trümper, Lorenz; Stein, Harald; Spang, Rainer; Esteller, Manel; Barker, David; Hasenclever, Dirk; Krebshilfe, Deutsche; Siebert, Reiner
New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling Journal Article
In: Blood, vol. 113, no. 11, pp. 2488–2497, 2009, ISSN: 0006-4971, 1528-0020.
@article{martin-subero_new_2009,
title = {New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling},
author = {José I. Martín-Subero and Markus Kreuz and Marina Bibikova and Stefan Bentink and Ole Ammerpohl and Eliza Wickham-Garcia and Maciej Rosolowski and Julia Richter and Lidia Lopez-Serra and Esteban Ballestar and Hilmar Berger and Xabier Agirre and Heinz-Wolfram Bernd and Vincenzo Calvanese and Sergio B. Cogliatti and Hans G. Drexler and Jian-Bing Fan and Mario F. Fraga and Martin L. Hansmann and Michael Hummel and Wolfram Klapper and Bernhard Korn and Ralf Küppers and Roderick A. F. MacLeod and Peter Möller and German Ott and Christiane Pott and Felipe Prosper and Andreas Rosenwald and Carsten Schwaenen and Dirk Schübeler and Marc Seifert and Benjamin Stürzenhofecker and Michael Weber and Swen Wessendorf and Markus Loeffler and Lorenz Trümper and Harald Stein and Rainer Spang and Manel Esteller and David Barker and Dirk Hasenclever and Deutsche Krebshilfe and Reiner Siebert},
url = {https://ashpublications.org/blood/article/113/11/2488/109977/New-insights-into-the-biology-and-origin-of-mature},
doi = {10.1182/blood-2008-04-152900},
issn = {0006-4971, 1528-0020},
year = {2009},
date = {2009-03-01},
urldate = {2025-09-18},
journal = {Blood},
volume = {113},
number = {11},
pages = {2488–2497},
abstract = {Abstract
Lymphomas are assumed to originate at different stages of lymphocyte development through chromosomal aberrations. Thus, different lymphomas resemble lymphocytes at distinct differentiation stages and show characteristic morphologic, genetic, and transcriptional features. Here, we have performed a microarray-based DNA methylation profiling of 83 mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) characterized for their morphologic, genetic, and transcriptional features, including molecular Burkitt lymphomas and diffuse large B-cell lymphomas. Hierarchic clustering indicated that methylation patterns in maB-NHLs were not strictly associated with morphologic, genetic, or transcriptional features. By supervised analyses, we identified 56 genes de novo methylated in all lymphoma subtypes studied and 22 methylated in a lymphoma subtype–specific manner. Remarkably, the group of genes de novo methylated in all lymphoma subtypes was significantly enriched for polycomb targets in embryonic stem cells. De novo methylated genes in all maB-NHLs studied were expressed at low levels in lymphomas and normal hematopoietic tissues but not in nonhematopoietic tissues. These findings, especially the enrichment for polycomb targets in stem cells, indicate that maB-NHLs with different morphologic, genetic, and transcriptional background share a similar stem cell–like epigenetic pattern. This suggests that maB-NHLs originate from cells with stem cell features or that stemness was acquired during lymphomagenesis by epigenetic remodeling.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lymphomas are assumed to originate at different stages of lymphocyte development through chromosomal aberrations. Thus, different lymphomas resemble lymphocytes at distinct differentiation stages and show characteristic morphologic, genetic, and transcriptional features. Here, we have performed a microarray-based DNA methylation profiling of 83 mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) characterized for their morphologic, genetic, and transcriptional features, including molecular Burkitt lymphomas and diffuse large B-cell lymphomas. Hierarchic clustering indicated that methylation patterns in maB-NHLs were not strictly associated with morphologic, genetic, or transcriptional features. By supervised analyses, we identified 56 genes de novo methylated in all lymphoma subtypes studied and 22 methylated in a lymphoma subtype–specific manner. Remarkably, the group of genes de novo methylated in all lymphoma subtypes was significantly enriched for polycomb targets in embryonic stem cells. De novo methylated genes in all maB-NHLs studied were expressed at low levels in lymphomas and normal hematopoietic tissues but not in nonhematopoietic tissues. These findings, especially the enrichment for polycomb targets in stem cells, indicate that maB-NHLs with different morphologic, genetic, and transcriptional background share a similar stem cell–like epigenetic pattern. This suggests that maB-NHLs originate from cells with stem cell features or that stemness was acquired during lymphomagenesis by epigenetic remodeling.
Lara, E; Mai, A; Calvanese, V; Altucci, L; Lopez-Nieva, P; Martinez-Chantar, M L; Varela-Rey, M; Rotili, D; Nebbioso, A; Ropero, S; Montoya, G; Oyarzabal, J; Velasco, S; Serrano, M; Witt, M; Villar-Garea, A; Inhof, A; Mato, J M; Esteller, M; Fraga, M F
Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect Journal Article
In: Oncogene, vol. 28, no. 6, pp. 781–791, 2009, ISSN: 0950-9232, 1476-5594.
@article{lara_salermide_2009,
title = {Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect},
author = {E Lara and A Mai and V Calvanese and L Altucci and P Lopez-Nieva and M L Martinez-Chantar and M Varela-Rey and D Rotili and A Nebbioso and S Ropero and G Montoya and J Oyarzabal and S Velasco and M Serrano and M Witt and A Villar-Garea and A Inhof and J M Mato and M Esteller and M F Fraga},
url = {https://www.nature.com/articles/onc2008436},
doi = {10.1038/onc.2008.436},
issn = {0950-9232, 1476-5594},
year = {2009},
date = {2009-02-01},
urldate = {2025-09-18},
journal = {Oncogene},
volume = {28},
number = {6},
pages = {781–791},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lara, E; Mai, A; Calvanese, V; Altucci, L; Lopez-Nieva, P; Martinez-Chantar, M L; Varela-Rey, M; Rotili, D; Nebbioso, A; Ropero, S; Montoya, G; Oyarzabal, J; Velasco, S; Serrano, M; Witt, M; Villar-Garea, A; Imhof, A; Mato, J M; Esteller, M; Fraga, M F
Erratum: Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect Journal Article
In: Oncogene, vol. 28, no. 8, pp. 1168–1168, 2009, ISSN: 0950-9232, 1476-5594.
@article{lara_erratum_2009,
title = {Erratum: Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect},
author = {E Lara and A Mai and V Calvanese and L Altucci and P Lopez-Nieva and M L Martinez-Chantar and M Varela-Rey and D Rotili and A Nebbioso and S Ropero and G Montoya and J Oyarzabal and S Velasco and M Serrano and M Witt and A Villar-Garea and A Imhof and J M Mato and M Esteller and M F Fraga},
url = {https://www.nature.com/articles/onc20091},
doi = {10.1038/onc.2009.1},
issn = {0950-9232, 1476-5594},
year = {2009},
date = {2009-02-01},
urldate = {2025-09-18},
journal = {Oncogene},
volume = {28},
number = {8},
pages = {1168–1168},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2008
Calvanese, Vincenzo; Horrillo, Angelica; Hmadcha, Abdelkrim; Suarez-Álvarez, Beatriz; Fernandez, Agustín F.; Lara, Ester; Casado, Sara; Menendez, Pablo; Bueno, Clara; Garcia-Castro, Javier; Rubio, Ruth; Lapunzina, Pablo; Alaminos, Miguel; Borghese, Lodovica; Terstegge, Stefanie; Harrison, Neil J.; Moore, Harry D.; Brüstle, Oliver; Lopez-Larrea, Carlos; Andrews, Peter W.; Soria, Bernat; Esteller, Manel; Fraga, Mario F.
Cancer Genes Hypermethylated in Human Embryonic Stem Cells Journal Article
In: PLoS ONE, vol. 3, no. 9, pp. e3294, 2008, ISSN: 1932-6203.
@article{calvanese_cancer_2008,
title = {Cancer Genes Hypermethylated in Human Embryonic Stem Cells},
author = {Vincenzo Calvanese and Angelica Horrillo and Abdelkrim Hmadcha and Beatriz Suarez-Álvarez and Agustín F. Fernandez and Ester Lara and Sara Casado and Pablo Menendez and Clara Bueno and Javier Garcia-Castro and Ruth Rubio and Pablo Lapunzina and Miguel Alaminos and Lodovica Borghese and Stefanie Terstegge and Neil J. Harrison and Harry D. Moore and Oliver Brüstle and Carlos Lopez-Larrea and Peter W. Andrews and Bernat Soria and Manel Esteller and Mario F. Fraga},
editor = {Maarten M. S. Van Lohuizen},
url = {https://dx.plos.org/10.1371/journal.pone.0003294},
doi = {10.1371/journal.pone.0003294},
issn = {1932-6203},
year = {2008},
date = {2008-09-01},
urldate = {2025-09-18},
journal = {PLoS ONE},
volume = {3},
number = {9},
pages = {e3294},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Calvanese, Vincenzo; Mallya, Meera; Campbell, R Duncan; Aguado, Begoña
Regulation of expression of two LY-6 family genes by intron retention and transcription induced chimerism Journal Article
In: BMC Molecular Biology, vol. 9, no. 1, pp. 81, 2008, ISSN: 1471-2199.
@article{calvanese_regulation_2008,
title = {Regulation of expression of two LY-6 family genes by intron retention and transcription induced chimerism},
author = {Vincenzo Calvanese and Meera Mallya and R Duncan Campbell and Begoña Aguado},
url = {http://bmcmolbiol.biomedcentral.com/articles/10.1186/1471-2199-9-81},
doi = {10.1186/1471-2199-9-81},
issn = {1471-2199},
year = {2008},
date = {2008-01-01},
urldate = {2025-09-18},
journal = {BMC Molecular Biology},
volume = {9},
number = {1},
pages = {81},
keywords = {},
pubstate = {published},
tppubtype = {article}
}