Journal
CELL STEM CELL
Volume 22, Issue 1, Pages 35-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2017.11.001
Keywords
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Funding
- Foundation of Aase and Ejnar Danielsen [10-001992]
- Axel Muusfeldts Foundation [2017-678]
- AIRC PI-Grant
- European Union's Horizon research and innovation programme [STEMHEALTH ERCCoG682665, INTENS 668294, DENOVOSTEM 670126]
- Worldwide Cancer Research [13-1216]
- Epigenetics Flagship projects (CNR-Miur grants)
- Ragnar Soderberg Foundation [N91/15]
- AIRC Special Program Molecular Clinical Oncology 5 per mille
- Carlsberg Foundation [CF14-0122]
- EMBO Young Investigator programme
- Lundbeck Foundation [R105-A9755]
- DFF mobilex programme [1333-00130B]
- Danish Cancer Society [R56-A2907, R124-A7724]
- Marie Curie fellowship programme [625238, 656099]
- Lundbeck Foundation [R105-2011-9755] Funding Source: researchfish
- Medical Research Council [MC_PC_12009] Funding Source: researchfish
- Novo Nordisk Fonden [NNF17OC0028730] Funding Source: researchfish
- Novo Nordisk Foundation Section for Basic Stem Cell Biology [Kim Jensen BasicStem affiliation] Funding Source: researchfish
- The Danish Cancer Society [R124-A7724] Funding Source: researchfish
- Marie Curie Actions (MSCA) [656099] Funding Source: Marie Curie Actions (MSCA)
- Grants-in-Aid for Scientific Research [17K19674] Funding Source: KAKEN
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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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