Long-Term Culture Captures Injury-Repair Cycles of Colonic Stem Cells.
Cell
; 179(5): 1144-1159.e15, 2019 11 14.
Article
en En
| MEDLINE
| ID: mdl-31708126
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Madre
/
Colon
/
Técnicas de Cultivo de Célula
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos