| Title: |
p53 promotes revival stem cells in the regenerating intestine after severe radiation injury |
| Authors: |
Clara Morral, Arshad Ayyaz, Hsuan-Cheng Kuo, Mardi Fink, Ioannis I. Verginadis, Andrea R. Daniel, Danielle N. 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 |
| Source: |
Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024) |
| Publisher Information: |
Nature Portfolio, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Science |
| Subject Terms: |
Science |
| More Details: |
Abstract Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced acute GI syndrome. Through single-cell RNA-sequencing of the irradiated mouse small intestine, we find that p53 target genes are specifically enriched in regenerating epithelial cells that undergo fetal-like reversion, including revival stem cells (revSCs) that promote animal survival after severe damage of the GI tract. Accordingly, in mice with p53 deleted specifically in the GI epithelium, ionizing radiation fails to induce fetal-like revSCs. Using intestinal organoids, we show that transient p53 expression is required for the induction of revival stem cells and is controlled by an Mdm2-mediated negative feedback loop. Together, our findings reveal that p53 suppresses severe radiation-induced GI injury by promoting fetal-like reprogramming of irradiated intestinal epithelial cells. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-47124-8 |
| Access URL: |
https://doaj.org/article/f8259dde53cf4c8bad036795c5ff982c |
| Accession Number: |
edsdoj.f8259dde53cf4c8bad036795c5ff982c |
| Database: |
Directory of Open Access Journals |
