| Literature DB >> 32449550 |
Buqing Ye1, Liuliu Yang1,2, Guomin Qian1,2, Benyu Liu1,2, Xiaoxiao Zhu3, Pingping Zhu1, Jing Ma4, Wei Xie4, Huimu Li1,2, Tianku Lu1,2, Yanying Wang1, Shuo Wang1, Ying Du1, Zhimin Wang1, Jing Jiang5, Jinsong Li5, Dongdong Fan3, Shu Meng3, Jiayi Wu1,2, Yong Tian2,3, Zusen Fan1,2.
Abstract
Lgr5+ intestinal stem cells (ISCs) exhibit self-renewal and differentiation features under homeostatic conditions, but the mechanisms controlling Lgr5 + ISC self-renewal remain elusive. Here, we show that the chromatin remodeler SRCAP is highly expressed in mouse intestinal epithelium and ISCs. Srcap deletion impairs both self-renewal of ISCs and intestinal epithelial regeneration. Mechanistically, SRCAP recruits the transcriptional regulator REST to the Prdm16 promoter and induces expression of this transcription factor. By activating PPARδ expression, Prdm16 in turn initiates PPARδ signaling, which sustains ISC stemness. Rest or Prdm16 deficiency abrogates the self-renewal capacity of ISCs as well as intestinal epithelial regeneration. Collectively, these data show that the SRCAP-REST-Prdm16-PPARδ axis is required for self-renewal maintenance of Lgr5 + ISCs.Entities:
Keywords: zzm321990RESTzzm321990; zzm321990SRCAPzzm321990; PPARδ; intestinal stem cell; self-renewal
Mesh：
Substances：
Year: 2020 PMID： 32449550 PMCID： PMC7327502 DOI： 10.15252/embj.2019103786
Source DB: PubMed Journal: EMBO J ISSN： 0261-4189 Impact factor: 11.598