Ezh1 Is Required for Hematopoietic Stem Cell Maintenance and Prevents Senescence-like Cell Cycle Arrest
Open accessAbstract
Polycomb group (PcG) proteins are key epigenetic regulators of hematopietic stem cell (HSC) fate. The PcG members Ezh2 and Ezh1 are important determinants of embryonic stem cell identity, and the transcript levels of these histone methyltransferases are inversely correlated during development. However, the role of Ezh1 in somatic stem cells is largely unknown. Here we show that Ezh1 maintains repopulating HSCs in a slow-cycling, undifferentiated state, protecting them from senescence. Ezh1 ablation induces significant loss of adult HSCs, with concomitant impairment of their self-renewal capacity due to a potent senescence response. Epigenomic and gene expression changes induced by Ezh1 deletion in senesced HSCs demonstrated that Ezh1-mediated PRC2 activity catalyzes monomethylation and dimethylation of H3K27. Deletion of Cdkn2a on the Ezh1 null background rescued HSC proliferation and survival. Our results suggest that Ezh1 is an important histone methyltransferase for HSC maintenance.
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HSCs are lost when EZH1 is ablated.
“HSCs are lost when EZH1 is ablated60.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [60]
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“It is worth noting in this light that, although deletion of Cdkn2a restores the proliferative potential of PRC2-deficient blood cells (Hidalgo et al., 2012), other defects remain, leading to stem-cell exhaustion, for example (Xie et al., 2014).”
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- Authors
- Hidalgo, I., Herrera-Merchan, A., Ligos, J. M., Carramolino, L., Nuñez, J., Martinez, F., Dominguez, O., Torres, M., & Gonzalez, S.
- Affiliations
- Spanish National Centre for Cardiovascular Research (ES)
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 11
- Issue
- 5
- Pages
- 649-662
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W1990646351
- Cited by
- 222
- References
- 6
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 4 · 2023: 12 · 2022: 22 · 2021: 12 · 2020: 17 · 2019: 22 · 2018: 16 · 2017: 14 · 2016: 24 · 2015: 22 · 2014: 23 · 2013: 17
- FWCI
- 13.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- EZH1, hematopoietic stem cells, Polycomb group proteins, polycomb repressive complex 2, H3K27 methylation, histone methyltransferase, cellular senescence, stem cell self-renewal, CDKN2A, epigenetic regulation, HSC maintenance
- MeSH terms
- Animals, Cell Differentiation, Hematopoietic Stem Cells, Methylation, Mice, Transgenic, Cellular Senescence, Genes, p16, Cell Proliferation, Mice, Cell Cycle Checkpoints, Polycomb Repressive Complex 2
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