The Histone Demethylases Jhdm1a/1b Enhance Somatic Cell Reprogramming in a Vitamin-C-Dependent Manner
Open accessAbstract
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) resets the epigenome to an embryonic-like state. Vitamin C enhances the reprogramming process, but the underlying mechanisms are unclear. Here we show that the histone demethylases Jhdm1a/1b are key effectors of somatic cell reprogramming downstream of vitamin C. We first observed that vitamin C induces H3K36me2/3 demethylation in mouse embryonic fibroblasts in culture and during reprogramming. We then identified Jhdm1a/1b, two known vitamin-C-dependent H3K36 demethylases, as potent regulators of reprogramming through gain- and loss-of-function approaches. Furthermore, we found that Jhdm1b accelerates cell cycle progression and suppresses cell senescence during reprogramming by repressing the Ink4/Arf locus. Jhdm1b also cooperates with Oct4 to activate the microRNA cluster 302/367, an integral component of the pluripotency machinery. Our results therefore reveal a role for H3K36me2/3 in cell fate determination and establish a link between histone demethylases and vitamin-C-induced reprogramming.
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Jumonji-C (JmjC) domain-containing proteins are responsible for hydroxylation of specific histone lysines leading to histone demethylation.
“One of the most known enzyme groups are Jumonji-C (JmjC) domain-containing proteins responsible for hydroxylation of specific histone lysines leading to histone demethylation (JmjC demethylases, e.g., JHDMs and KDMs families) [107,112,113,114].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [112]
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- Authors
- Wang, T., Chen, K., Zeng, X., Yang, J., Wu, Y., Shi, X., Qin, B., Zeng, L., Esteban, M. A., Pan, G., & Pei, D.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Pei, Duanqing
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 9
- Issue
- 6
- Pages
- 575-587
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2020423861
- Cited by
- 458
- References
- 5
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 14 · 2023: 32 · 2022: 23 · 2021: 39 · 2020: 35 · 2019: 30 · 2018: 28 · 2017: 28 · 2016: 32 · 2015: 44 · 2014: 38 · 2013: 54 · 2012: 37
- FWCI
- 16.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 594 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- histone demethylase, somatic cell reprogramming, induced pluripotent stem cells, vitamin C, INK4/ARF locus, cellular senescence, cell cycle progression, Oct4, pluripotency, epigenetic reprogramming
- MeSH terms
- Animals, Antioxidants, Ascorbic Acid, Cell Cycle, Cells, Cultured, Fibroblasts, Histones, Humans, Lysine, Mice, Transgenic, Cellular Senescence, Pluripotent Stem Cells, F-Box Proteins, Octamer Transcription Factor-3, Mice, Jumonji Domain-Containing Histone Demethylases, Cellular Reprogramming
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