| Literature DB >> 32839595 |
Linpeng Li1,2, Keshi Chen1,2, Tianyu Wang1,2, Yi Wu1,2, Guangsuo Xing1,2, Mengqi Chen1,2, Zhihong Hao1,2, Cheng Zhang3, Jinye Zhang3, Bochao Ma1,2, Zihuang Liu1,2, Hao Yuan1,2, Zijian Liu1,2, Qi Long1,2, Yanshuang Zhou1,2, Juntao Qi1,2, Danyun Zhao1,2, Mi Gao1,2, Duanqing Pei1,2, Jinfu Nie1,2, Dan Ye3, Guangjin Pan1,2, Xingguo Liu4,5.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2020 PMID： 32839595 DOI： 10.1038/s42255-020-0267-9
Source DB: PubMed Journal: Nat Metab ISSN： 2522-5812