Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium

Tsunaki Higa, Yasutaka Okita, Akinobu Matsumoto, Shogo Nakayama, Takeru Oka, Osamu Sugahara, Daisuke Koga, Shoichiro Takeishi, Hirokazu Nakatsumi, Naoki Hosen, Sylvie Robine, Makoto M. Taketo, Toshiro Sato, Keiichi I. Nakayama

研究成果: Article査読

抄録

Although the mammalian intestinal epithelium manifests robust regenerative capacity after various cytotoxic injuries, the underlying mechanism has remained unclear. Here we identify the cyclin-dependent kinase inhibitor p57 as a specific marker for a quiescent cell population located around the +4 position of intestinal crypts. Lineage tracing reveals that the p57+ cells serve as enteroendocrine/tuft cell precursors under normal conditions but dedifferentiate and act as facultative stem cells to support regeneration after injury. Single-cell transcriptomics analysis shows that the p57+ cells undergo a dynamic reprogramming process after injury that is characterized by fetal-like conversion and metaplasia-like transformation. Population-level analysis also detects such spatiotemporal reprogramming widely in other differentiated cell types. In intestinal adenoma, p57+ cells manifest homeostatic stem cell activity, in the context of constitutively activated spatiotemporal reprogramming. Our results highlight a pronounced plasticity of the intestinal epithelium that supports maintenance of tissue integrity in normal and neoplastic contexts.

本文言語English
論文番号1500
ジャーナルNature communications
13
1
DOI
出版ステータスPublished - 2022 12月

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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