TY - JOUR

T1 - YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration

AU - Yui, Shiro

AU - Azzolin, Luca

AU - Maimets, Martti

AU - Pedersen, Marianne Terndrup

AU - Fordham, Robert P.

AU - Hansen, Stine L.

AU - Larsen, Hjalte L.

AU - Guiu, Jordi

AU - Alves, Mariana R.P.

AU - Rundsten, Carsten F.

AU - Johansen, Jens V.

AU - Li, Yuan

AU - Madsen, Chris D.

AU - Nakamura, Tetsuya

AU - Watanabe, Mamoru

AU - Nielsen, Ole H.

AU - Schweiger, Pawel J.

AU - Piccolo, Stefano

AU - Jensen, Kim B.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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. The mechanism that governs tissue regeneration following severe damage to the colonic epithelium remains poorly understood. Jensen and colleagues show that the colonic epithelium undergoes a profound reprogramming into a more primitive state with fetal-like properties. Moreover, they demonstrate that YAP and TAZ operate as essential mechano-sensors during tissue reprogramming.

AB - 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. The mechanism that governs tissue regeneration following severe damage to the colonic epithelium remains poorly understood. Jensen and colleagues show that the colonic epithelium undergoes a profound reprogramming into a more primitive state with fetal-like properties. Moreover, they demonstrate that YAP and TAZ operate as essential mechano-sensors during tissue reprogramming.

KW - Intestinal stem cells

KW - Mechano-sensing

KW - Regeneration

KW - Reprogramming

KW - YAP/TAZ

U2 - 10.1016/j.stem.2017.11.001

DO - 10.1016/j.stem.2017.11.001

M3 - Journal article

C2 - 29249464

AN - SCOPUS:85039042378

VL - 22

SP - 35-49. e7

JO - Cell Stem Cell

JF - Cell Stem Cell

SN - 1934-5909

IS - 1

ER -