The E3 ubiquitin ligase function of the epigenetic reader PHF16 is crucial for injury-induced intestinal regeneration

The intestine has a remarkable capacity to regenerate during homeostasis by the vigorous intestinal stem cells (ISCs) that reside in the base of the crypts. ISCs are easily impaired by DNA damage due to their active cell cycle. Intriguingly, certain cell populations possess the dedifferentiating ability to restore ISCs after ablation, although the molecular mechanisms by which these cells dedifferentiate into ISCs are largely unknown. Here, we performed single-cell RNA-seq using wild type and Phf16 knockout mice from normal or after irradiation to elucidate molecular mechanisms of Phf16 in intestinal regeneration. Our work characterizes that Phf16 is crucial for downregulating stemness in revival stem cells.

肠道在机体稳态过程中，依托位于肠隐窝基底的活跃肠干细胞（intestinal stem cells，ISCs）具备极强的再生能力。由于肠干细胞处于活跃的细胞周期中，其极易受到DNA损伤的侵袭。有趣的是，部分细胞群在肠干细胞被清除后可通过去分化能力修复肠干细胞，尽管此类细胞向肠干细胞转化的分子机制目前仍未明确。本研究借助正常状态及辐照后的野生型与Phf16基因敲除小鼠，开展单细胞RNA测序（single-cell RNA-seq）以阐明Phf16在肠道再生过程中的分子调控机制。本研究证实，Phf16对抑制复苏干细胞的干细胞干性至关重要。