Characterization of radioresistant epithelial stem cell heterogeneity in the damaged mouse intestine

Taku Sato, Miwako Sase, Shun Ishikawa, Mihoko Kajita, Jumpei Asano, Toshiro Sato, Yoshiyuki Mori, Toshiaki Ohteki

研究成果: Article査読

抄録

The small intestine has a robust regenerative capacity, and various cell types serve as “cells-of-origin” in the epithelial regeneration process after injury. However, how much each population contributes to regeneration remains unclear. Using lineage tracing, we found that Lgr5-expressing cell derivatives contained radioresistant intestinal stem cells (ISCs) crucial for epithelial regeneration in the damaged intestine after irradiation. Single-cell qRT-PCR analysis showed that surviving Lgr5-expressing cell derivatives in the damaged intestine are remarkably heterogeneous, and that the expression levels of a YAP-target gene Sca1 were inversely correlated with their “stemness”, suggesting that the YAP/Wnt signal balance in surviving crypt epithelial cells determines the cellular contribution to epithelial regeneration. Single-cell RNA sequencing of Sca1Lgr5-derivatives revealed that expression of a tetraspanin family member CD81 correlated well with the expression of ISC- and proliferation-related genes. Consistent with these findings, organoid-forming ability was confined to the CD81hiSca1 fraction within the damaged crypt epithelial cells. Characterization of radioresistant epithelial stem cell heterogeneity in the damaged intestine may contribute to therapeutic strategies for gastrointestinal diseases.

本文言語English
論文番号8308
ジャーナルScientific reports
10
1
DOI
出版ステータスPublished - 2020 12 1

ASJC Scopus subject areas

  • General

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