1. Long-Term Culture Captures Injury-Repair Cycles of Colonic Stem Cells.
- Author
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Wang Y, Chiang IL, Ohara TE, Fujii S, Cheng J, Muegge BD, Ver Heul A, Han ND, Lu Q, Xiong S, Chen F, Lai CW, Janova H, Wu R, Whitehurst CE, VanDussen KL, Liu TC, Gordon JI, Sibley LD, and Stappenbeck TS
- Subjects
- 3T3 Cells, Animals, Colitis pathology, Epithelial Cells drug effects, Epithelial Cells pathology, Homeodomain Proteins metabolism, Mice, Models, Biological, Oxygen pharmacology, Regeneration drug effects, Stem Cells drug effects, Stress, Physiological drug effects, Cell Culture Techniques methods, Colon pathology, Stem Cells pathology
- Abstract
The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hopx
+ colitis-associated regenerative stem cell (CARSC) population that functionally contributes to mucosal repair in mouse models of colitis. Hopx+ CARSCs, enriched for fetal-like markers, transiently arose from hypertrophic crypts known to facilitate regeneration. Importantly, we established a long-term, self-organizing two-dimensional (2D) epithelial monolayer system to model the regenerative properties and responses of Hopx+ CARSCs. This system can reenact the "homeostasis-injury-regeneration" cycles of epithelial alterations that occur in vivo. Using this system, we found that hypoxia and endoplasmic reticulum stress, insults commonly present in inflammatory bowel diseases, mediated the cyclic switch of cellular status in this process., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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