干细胞
肠上皮
生物
细胞生物学
上皮
胃肠上皮
再生(生物学)
癌症研究
电离辐射
小肠
重编程
地穴
细胞
内分泌学
辐照
遗传学
物理
核物理学
作者
Clara Morral,Arshad Ayyaz,Hsuan-Cheng Kuo,Mardi Fink,Ioannis I. Verginadis,Andrea R. Daniel,Danielle Burner,Lucy M. Driver,Sloane Satow,Stephanie Hasapis,Reem Ghinnagow,Lixia Luo,Yan Ma,Laura D. Attardi,Constantinos Koumenis,Andy J. Minn,Jeffrey L. Wrana,Chang-Lung Lee,David G. Kirsch
标识
DOI:10.1101/2023.04.27.538576
摘要
Abstract Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced GI injury. Through single-cell RNA-sequencing of the irradiated mouse intestine, we find that p53 target genes are specifically enriched in stem cells of the regenerating epithelium, including revival stem cells that promote animal survival after GI damage. Accordingly, in mice with p53 deleted specifically in the GI epithelium, ionizing radiation fails to induce revival stem cells. Using intestinal organoids, we show that transient p53 expression is required for the induction of revival stem cells that is controlled by an Mdm2-mediated negative feedback loop. These results suggest that p53 suppresses severe radiation-indued GI injury by promoting intestinal epithelial cell reprogramming. One-Sentence Summary After severe radiation injury to the intestine, transient p53 activity induces revival stem cells to promote regeneration.
科研通智能强力驱动
Strongly Powered by AbleSci AI