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2016 ; 14
(10
): 2301-12
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YAP Induces Human Naive Pluripotency
#MMPMID26947063
Qin H
; Hejna M
; Liu Y
; Percharde M
; Wossidlo M
; Blouin L
; Durruthy-Durruthy J
; Wong P
; Qi Z
; Yu J
; Qi LS
; Sebastiano V
; Song JS
; Ramalho-Santos M
Cell Rep
2016[Mar]; 14
(10
): 2301-12
PMID26947063
show ga
The human naive pluripotent stem cell (PSC) state, corresponding to a
pre-implantation stage of development, has been difficult to capture and sustain
in vitro. We report that the Hippo pathway effector YAP is nuclearly localized in
the inner cell mass of human blastocysts. Overexpression of YAP in human
embryonic stem cells (ESCs) and induced PSCs (iPSCs) promotes the generation of
naive PSCs. Lysophosphatidic acid (LPA) can partially substitute for YAP to
generate transgene-free human naive PSCs. YAP- or LPA-induced naive PSCs have a
rapid clonal growth rate, a normal karyotype, the ability to form teratomas,
transcriptional similarities to human pre-implantation embryos, reduced
heterochromatin levels, and other hallmarks of the naive state. YAP/LPA act in
part by suppressing differentiation-inducing effects of GSK3 inhibition.
CRISPR/Cas9-generated YAP(-/-) cells have an impaired ability to form colonies in
naive but not primed conditions. These results uncover an unexpected role for YAP
in the human naive state, with implications for early human embryology.
|Adaptor Proteins, Signal Transducing/antagonists &
inhibitors/genetics/*metabolism
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