@article{3cee17aa11ee4c73a09c188b904302c9,
title = "Long-Term Culture Captures Injury-Repair Cycles of Colonic Stem Cells",
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.",
keywords = "HopX, Lgr5, Transwell, air-liquid interface, colitis, colon, hypoxia, intestine, stem cell, unfolded protein response",
author = "Yi Wang and Chiang, {I. Ling} and Ohara, {Takahiro E.} and Satoru Fujii and Jiye Cheng and Muegge, {Brian D.} and {Ver Heul}, Aaron and Han, {Nathan D.} and Qiuhe Lu and Shanshan Xiong and Feidi Chen and Lai, {Chin Wen} and Hana Janova and Renee Wu and Whitehurst, {Charles E.} and VanDussen, {Kelli L.} and Liu, {Ta Chiang} and Gordon, {Jeffrey I.} and Sibley, {L. David} and Stappenbeck, {Thaddeus S.}",
note = "Funding Information: We acknowledge the Washington University in St. Louis facilities (DDRCC, GTAC, Siteman Cancer Center Flow Core) and WUCCI. Bill and Melinda Gates Foundation ( OPP1098828 , OPP1139330 ), Crohn's & Colitis Foundation , NIH ( DK30292 ), and Boehringer-Ingelheim provided support. Funding Information: We acknowledge the Washington University in St. Louis facilities (DDRCC, GTAC, Siteman Cancer Center Flow Core) and WUCCI. Bill and Melinda Gates Foundation (OPP1098828, OPP1139330), Crohn's & Colitis Foundation, NIH (DK30292), and Boehringer-Ingelheim provided support. Y.W. J.I.G. and T.S.S. designed experiments and wrote the manuscript. L.D.S. T.-C.L. and C.E.W. designed experiments. Y.W. I.-L.C. T.E.O. S.F. J.C. A.V.H. N.D.H. Q.L. S.X. F.C. C.-W.L. H.J. R.W. B.D.M. and K.L.V. performed experiments and analyzed data. All authors edited the manuscript. T.S.S. has served on an advisory board for Boehringer Ingelheim. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = nov,
day = "14",
doi = "10.1016/j.cell.2019.10.015",
language = "English",
volume = "179",
pages = "1144--1159.e15",
journal = "Cell",
issn = "0092-8674",
number = "5",
}