The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells. Academic Article uri icon

Overview

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.

publication date

  • May 25, 2020

Research

keywords

  • Adenosine Triphosphatases
  • Intestinal Mucosa
  • Signal Transduction
  • Stem Cells

Identity

PubMed Central ID

  • PMC7327502

Scopus Document Identifier

  • 85085593437

Digital Object Identifier (DOI)

  • 10.15252/embj.2019103786

PubMed ID

  • 32449550

Additional Document Info

volume

  • 39

issue

  • 13