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
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View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsThis monoclonal targets CD31 (PECAM-1)
View all literature mentionsThis monoclonal targets CD326 (EpCAM)
View all literature mentionsThis polyclonal secondary targets IgG2a
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse TROP-2
View all literature mentionsThis monoclonal targets Mouse Reg IIIb
View all literature mentionsThis polyclonal targets Mouse LRIG1 Affinity Purified Ab
View all literature mentionsThis unknown targets Mucin 2
View all literature mentionsThis polyclonal targets Ki67 antibody - Proliferation Marker
View all literature mentionsThis polyclonal targets Lysozyme
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View all literature mentionsThis monoclonal targets E-CADHERIN
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View all literature mentionsThis unknown targets Annexin A1
View all literature mentionsThis monoclonal targets Mouse Sca-1 / Ly6
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