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2014 ; 157
(6
): 1324-1338
Nephropedia Template TP
Yimlamai D
; Christodoulou C
; Galli GG
; Yanger K
; Pepe-Mooney B
; Gurung B
; Shrestha K
; Cahan P
; Stanger BZ
; Camargo FD
Cell
2014[Jun]; 157
(6
): 1324-1338
PMID24906150
show ga
The Hippo-signaling pathway is an important regulator of cellular proliferation
and organ size. However, little is known about the role of this cascade in the
control of cell fate. Employing a combination of lineage tracing, clonal
analysis, and organoid culture approaches, we demonstrate that Hippo pathway
activity is essential for the maintenance of the differentiated hepatocyte state.
Remarkably, acute inactivation of Hippo pathway signaling in vivo is sufficient
to dedifferentiate, at very high efficiencies, adult hepatocytes into cells
bearing progenitor characteristics. These hepatocyte-derived progenitor cells
demonstrate self-renewal and engraftment capacity at the single-cell level. We
also identify the NOTCH-signaling pathway as a functional important effector
downstream of the Hippo transducer YAP. Our findings uncover a potent role for
Hippo/YAP signaling in controlling liver cell fate and reveal an unprecedented
level of phenotypic plasticity in mature hepatocytes, which has implications for
the understanding and manipulation of liver regeneration.
|*Cell Dedifferentiation
[MESH]
|*Signal Transduction
[MESH]
|Adaptor Proteins, Signal Transducing/metabolism
[MESH]
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