YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration. (original) (raw)
Searching across hundreds of databases
Our searching services are busy right now. Please try again later
X
Forgot Password
If you have forgotten your password you can enter your email here and get a temporary password sent to your email.
X
Forgot Password
If you have forgotten your password you can enter your email here and get a temporary password sent to your email.
Cell stem cell | 2018
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.
Pubmed ID: 29249464 RIS Download
Research resources used in this publication
None found
Additional research tools detected in this publication
None found
Antibodies used in this publication
None found
Associated grants
- Agency: Worldwide Cancer Research, United Kingdom
Id: 13-1216 - Agency: European Research Council, International
Id: 670126 - Agency: Medical Research Council, United Kingdom
Id: MC_PC_12009