YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration.
Cell Stem Cell
; 22(1): 35-49.e7, 2018 01 04.
Article
em En
| MEDLINE
| ID: mdl-29249464
ABSTRACT
Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state. This is characterized by de novo expression of fetal markers as well as suppression of markers for adult stem and differentiated cells. The fate change is orchestrated by remodeling the extracellular matrix (ECM), increased FAK/Src signaling, and ultimately YAP/TAZ activation. In a defined cell culture system recapitulating the extracellular matrix remodeling observed in vivo, we show that a collagen 3D matrix supplemented with Wnt ligands is sufficient to sustain endogenous YAP/TAZ and induce conversion of cell fate. This provides a simple model for tissue regeneration, implicating cellular reprogramming as an essential element.
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MEDLINE
Assunto principal:
Fosfoproteínas
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Regeneração
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Proteínas Adaptadoras de Transdução de Sinal
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Matriz Extracelular
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Reprogramação Celular
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Mucosa Intestinal
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article