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YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration

Yui, Shiro; Azzolin, Luca; Maimets, Martti; Pedersen, Marianne Terndrup; Fordham, Robert P; Hansen, Stine L; Larsen, Hjalte L; Guiu, Jordi; Alves, Mariana R P and Rundsten, Carsten F, et al. (2018) In Cell Stem Cell 22(1). p.7-49
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... (More)

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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Journal Article
in
Cell Stem Cell
volume
22
issue
1
pages
7 - 49
publisher
Cell Press
external identifiers
  • scopus:85039042378
ISSN
1934-5909
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English
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39e800f0-be73-43da-9a6b-181f7acc4795
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2017-12-19 12:20:11
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2018-06-10 05:25:44
@article{39e800f0-be73-43da-9a6b-181f7acc4795,
  abstract     = {<p>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.</p>},
  author       = {Yui, Shiro and Azzolin, Luca and Maimets, Martti and Pedersen, Marianne Terndrup and Fordham, Robert P and Hansen, Stine L and Larsen, Hjalte L and Guiu, Jordi and Alves, Mariana R P and Rundsten, Carsten F and Johansen, Jens V and Li, Yuan and Madsen, Chris D and Nakamura, Tetsuya and Watanabe, Mamoru and Nielsen, Ole H and Schweiger, Pawel J and Piccolo, Stefano and Jensen, Kim B},
  issn         = {1934-5909},
  keyword      = {Journal Article},
  language     = {eng},
  number       = {1},
  pages        = {7--49},
  publisher    = {Cell Press},
  series       = {Cell Stem Cell},
  title        = {YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration},
  url          = {http://dx.doi.org/},
  volume       = {22},
  year         = {2018},
}