p53 promotes revival stem cells in the regenerating intestine after severe radiation injury

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 () and David G. Kirsch ()
Additional contact information
Clara Morral: University of Pennsylvania
Arshad Ayyaz: Mount Sinai Hospital
Hsuan-Cheng Kuo: Duke University
Mardi Fink: Mount Sinai Hospital
Ioannis I. Verginadis: University of Pennsylvania
Andrea R. Daniel: Duke University
Danielle N. Burner: Duke University
Lucy M. Driver: Duke University
Sloane Satow: Duke University
Stephanie Hasapis: Duke University
Reem Ghinnagow: University of Pennsylvania
Lixia Luo: Duke University
Yan Ma: Duke University
Laura D. Attardi: Stanford University
Constantinos Koumenis: University of Pennsylvania
Andy J. Minn: University of Pennsylvania
Jeffrey L. Wrana: Mount Sinai Hospital
Chang-Lung Lee: Duke University
David G. Kirsch: Duke University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47124-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47124-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47124-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().