Cycling Stem Cells Are Radioresistant and Regenerate the Intestine

Xiaole Sheng, Ziguang Lin, Cong Lv, Chunlei Shao, Xueyun Bi, Min Deng, Jiuzhi Xu, Christian F. Guerrero-Juarez, Mengzhen Li, Xi Wu, Ran Zhao, Xu Yang, Guilin Li, Xiaowei Liu, Qingyu Wang, Qing Nie, Wei Cui, Shan Gao, Hongquan Zhang, Zhihua LiuYingzi Cong, Maksim V. Plikus, Christopher J. Lengner, Bogi Andersen, Fazheng Ren, Zhengquan Yu

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

A certain number of epithelial cells in intestinal crypts are DNA damage resistant and contribute to regeneration. However, the cellular mechanism underlying intestinal regeneration remains unclear. Using lineage tracing, we show that cells marked by an Msi1 reporter (Msi1+) are right above Lgr5high cells in intestinal crypts and exhibit DNA damage resistance. Single-cell RNA sequencing reveals that the Msi1+ cells are heterogeneous with the majority being intestinal stem cells (ISCs). The DNA damage-resistant subpopulation of Msi1+ cells is characterized by low-to-negative Lgr5 expression and is more rapidly cycling than Lgr5high radiosensitive crypt base columnar stem cells (CBCs). This enables an efficient repopulation of the intestinal epithelium at early stage when Lgr5high cells are not emerging. Furthermore, relative to CBCs, Msi1+ cells preferentially produce Paneth cells during homeostasis and upon radiation repair. Together, we demonstrate that the DNA damage-resistant Msi1+ cells are cycling ISCs that maintain and regenerate the intestinal epithelium.

Original languageEnglish (US)
Article number107952
JournalCell Reports
Volume32
Issue number4
DOIs
StatePublished - Jul 28 2020

Keywords

  • DNA damage response
  • Msi1
  • epithelial regeneration
  • intestinal stem cells

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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