期刊
NATURE METABOLISM
卷 2, 期 9, 页码 882-+出版社
NATURE RESEARCH
DOI: 10.1038/s42255-020-0267-9
关键词
-
资金
- National Key Research and Development Program of China [2017YFA0106300, 2017YFA0102900, 2017YFC1001602, 2019YFA09004500, 2016YFA0100300, 2018YFA0107100]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16030505]
- National Natural Science Foundation projects of China [U1601227, 31631163001, 31701281, 31701106, 31801168, 31900614, 31970709, 81901275]
- Key Research Program of Frontier Sciences, Chinese Academy of Sciences (CAS) [QYZDB-SSW-SMC001]
- CAS STS Program [KFJ-STS-QYZD-125]
- Guangzhou Health Care and Cooperative Innovation Major Project [201704020218]
- Guangdong Province Science and Technology Program [2017B020230005, 2017A020215056, 2017B030314056, 2018A030313825, 2018GZR110103002, 2020A1515011200, 2020A1515010919, 2020A1515011410]
- Guangzhou Science and Technology Program [201707010178, 201807010067, 202002030277]
- Yangtse River Scholar Bonus Schemes
- CAS Youth Innovation Promotion Association
Somatic cell reprogramming provides insight into basic principles of cell fate determination, which remain poorly understood. Here we show that the transcription factor Glis1 induces multi-level epigenetic and metabolic remodelling in stem cells that facilitates the induction of pluripotency. We find that Glis1 enables reprogramming of senescent cells into pluripotent cells and improves genome stability. During early phases of reprogramming, Glis1 directly binds to and opens chromatin at glycolytic genes, whereas it closes chromatin at somatic genes to upregulate glycolysis. Subsequently, higher glycolytic flux enhances cellular acetyl-CoA and lactate levels, thereby enhancing acetylation (H3K27Ac) and lactylation (H3K18la) at so-called 'second-wave' and pluripotency gene loci, opening them up to facilitate cellular reprogramming. Our work highlights Glis1 as a powerful reprogramming factor, and reveals an epigenome-metabolome-epigenome signalling cascade that involves the glycolysis-driven coordination of histone acetylation and lactylation in the context of cell fate determination.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据