Atoh1+ secretory progenitors possess renewal capacity independent of Lgr5+ cells during colonic regeneration.
EMBO J
; 38(4)2019 02 15.
Article
em En
| MEDLINE
| ID: mdl-30635334
ABSTRACT
During homeostasis, the colonic epithelium is replenished every 3-5 days by rapidly cycling Lgr5+ stem cells. However, various insults can lead to depletion of Lgr5+ stem cells, and colonic epithelium can be regenerated from Lgr5-negative cells. While studies in the small intestine have addressed the lineage identity of the Lgr5-negative regenerative cell population, in the colon this question has remained unanswered. Here, we set out to identify which cell(s) contribute to colonic regeneration by performing genetic fate-mapping studies of progenitor populations in mice. First, using keratin-19 (Krt19) to mark a heterogeneous population of cells, we found that Lgr5-negative cells can regenerate colonic crypts and give rise to Lgr5+ stem cells. Notch1+ absorptive progenitor cells did not contribute to epithelial repair after injury, whereas Atoh1+ secretory progenitors did contribute to this process. Additionally, while colonic Atoh1+ cells contributed minimally to other lineages during homeostasis, they displayed plasticity and contributed to epithelial repair during injury, independent of Lgr5+ cells. Our findings suggest that promotion of secretory progenitor plasticity could enable gut healing in colitis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Células-Tronco
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Colite
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Colo
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Receptores Acoplados a Proteínas G
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Intestino Delgado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article