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Record W4394570486 · doi:10.1038/s41467-024-47124-8

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

2024· article· en· W4394570486 on OpenAlexaff
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

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldMedicine
TopicCancer Cells and Metastasis
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoLunenfeld-Tanenbaum Research InstituteUniversity of CalgaryMount Sinai Hospital
FundersNational Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesSchool of Medicine, Duke UniversityNational Cancer InstituteU.S. Department of Health and Human ServicesNational Institutes of HealthPerelman School of Medicine, University of PennsylvaniaMark Foundation For Cancer ResearchUniversity of Pennsylvania
KeywordsStem cellBiologyIntestinal epitheliumIonizing radiationEpitheliumGastrointestinal tractCancer researchCell biologySmall intestineGastrointestinal epitheliumReprogrammingCellIrradiationEndocrinologyGenetics

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.868
Threshold uncertainty score0.487

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.024
GPT teacher head0.323
Teacher spread0.299 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations51
Published2024
Admission routes1
Has abstractyes

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