The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells.
Buqing YeLiuliu YangGuomin QianBenyu LiuXiaoxiao ZhuPingping ZhuJing MaWei XieHuimu LiTianku LuYanying WangShuo WangYing DuZhimin WangJing JiangJinsong LiDongdong FanShu MengJiayi WuYong TianZusen FanPublished in: The EMBO journal (2020)
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.
Keyphrases
- stem cells
- transcription factor
- gene expression
- poor prognosis
- insulin resistance
- dna damage
- cell therapy
- signaling pathway
- dna methylation
- fatty acid
- genome wide
- metabolic syndrome
- dna binding
- mesenchymal stem cells
- big data
- bone marrow
- heat shock
- quantum dots
- long non coding rna
- skeletal muscle
- smoking cessation
- artificial intelligence
- fluorescent probe
- data analysis