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The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells.
Ye, Buqing; Yang, Liuliu; Qian, Guomin; Liu, Benyu; Zhu, Xiaoxiao; Zhu, Pingping; Ma, Jing; Xie, Wei; Li, Huimu; Lu, Tianku; Wang, Yanying; Wang, Shuo; Du, Ying; Wang, Zhimin; Jiang, Jing; Li, Jinsong; Fan, Dongdong; Meng, Shu; Wu, Jiayi; Tian, Yong; Fan, Zusen.
Affiliation
  • Ye B; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Yang L; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Qian G; University of Chinese Academy of Sciences, Beijing, China.
  • Liu B; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Zhu X; University of Chinese Academy of Sciences, Beijing, China.
  • Zhu P; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Ma J; University of Chinese Academy of Sciences, Beijing, China.
  • Xie W; Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Li H; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Lu T; MOE Key Laboratory of Bioinformatics, Center for Stem Cell Biology and Regenerative Medicine, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Wang Y; MOE Key Laboratory of Bioinformatics, Center for Stem Cell Biology and Regenerative Medicine, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Wang S; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Du Y; University of Chinese Academy of Sciences, Beijing, China.
  • Wang Z; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Jiang J; University of Chinese Academy of Sciences, Beijing, China.
  • Li J; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Fan D; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Meng S; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Wu J; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Tian Y; State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Genome Tagging Project (GTP) Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences,
  • Fan Z; State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Genome Tagging Project (GTP) Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences,
EMBO J ; 39(13): e103786, 2020 07 01.
Article in En | MEDLINE | ID: mdl-32449550
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stem Cells / Signal Transduction / Adenosine Triphosphatases / Intestinal Mucosa Limits: Animals / Humans Language: En Journal: EMBO J Year: 2020 Type: Article Affiliation country: China
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stem Cells / Signal Transduction / Adenosine Triphosphatases / Intestinal Mucosa Limits: Animals / Humans Language: En Journal: EMBO J Year: 2020 Type: Article Affiliation country: China