HOPX+ injury-resistant intestinal stem cells drive epithelial recovery after severe intestinal ischemia
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 321(5), G588–G602.
author keywords: epithelial repair; HOPX; ischemia; large animal models; stem cell
MeSH headings : Animals; Cell Proliferation; Disease Models, Animal; Epithelial Cells / metabolism; Epithelial Cells / pathology; Female; Homeodomain Proteins / genetics; Homeodomain Proteins / metabolism; Intestinal Mucosa / metabolism; Intestinal Mucosa / pathology; Male; Mesenteric Ischemia / genetics; Mesenteric Ischemia / metabolism; Mesenteric Ischemia / pathology; Phenotype; Re-Epithelialization; Severity of Illness Index; Stem Cells / metabolism; Stem Cells / pathology; Sus scrofa; Tissue Culture Techniques
TL;DR:
It is demonstrated that during early in vivo recovery, injury-resistant HOPX+cells maintain quiescence, suggesting that HopX may serve a functional role in ISC mediated regeneration after injury and could be a target to control ISC proliferation.
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This paper supports that rISCs are resistant to ischemic injury and likely an important source of cellular renewal following near-complete epithelial loss. Furthermore, we have evidence that HOPX controls ISC activity state and may be a critical signaling pathway during ISC-mediated repair. Finally, we use multiple novel methods to evaluate ISCs in a translationally relevant large animal model of severe intestinal injury and provide evidence for the potential role of rISCs as therapeutic targets.