Language

English

Publication Date

10-30-2025

Journal

American Journal of Physiology: Gastrointestinal and Liver Physiology

DOI

10.1152/ajpgi.00186.2025

PMID

41165566

Abstract

Radiation exposure impairs rapidly renewing tissues like the intestinal epithelium, yet translational insights from murine models have been limited by species-specific responses. Here, we use human intestinal organoids (HIOs) derived from jejunal epithelium to evaluate human epithelial responses to low dose proton and photon (gamma) radiation. Gamma irradiation induces a unique developmental and metabolic shift in crypt-like organoids, including enrichment of amino acid metabolism pathways and activation of fetal-associated transcription factors and morphology. Integrated multi-omic profiling reveals serotonin biosynthesis as a central regenerative node. Human intestinal organoids can complement animal models and are emerging as a powerful tool in modeling human radiation responses and identifying candidate biomarkers for intestinal injury.

Keywords

: intestine, organoid, radiation, stem cell reversion

Published Open-Access

yes

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