Lgr5⁺ intestinal stem cells (ISC s) 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 ISC s. Srcap deletion impairs both self‐renewal of ISC s and intestinal epithelial regeneration. Mechanistically, SRCAP recruits the transcriptional regulator REST to the Prdm16 promoter and induces expression of this transcription factor. By activating PPAR δ expression, Prdm16 in turn initiates PPAR δ signaling, which sustains ISC stemness. Rest or Prdm16 deficiency abrogates the self‐renewal capacity of ISC s as well as intestinal epithelial regeneration. Collectively, these data show that the SRCAP ‐REST ‐Prdm16‐PPAR δ axis is required for self‐renewal maintenance of Lgr5 + ISC s.

中文翻译：

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染色质重塑剂SRCAP促进肠道干细胞的自我更新。

Lgr5 ⁺肠道干细胞（ISC）在稳态条件下表现出自我更新和分化的特征，但是控制Lgr5 + ISC自我更新的机制仍然难以捉摸。在这里，我们表明染色质重塑剂SRCAP在小鼠肠上皮和ISC中高度表达。Srcap缺失会损害ISC的自我更新和肠道上皮再生。从机理上讲，SRCAP将转录调节因子REST募集到Prdm16启动子，并诱导该转录因子的表达。通过激活PPARδ表达，Prdm16继而启动PPARδ信号传导，维持ISC的干性。休息或Prdm16缺乏会消除ISC的自我更新能力以及肠上皮再生。总的来说，