TY - JOUR
T1 - YAP Induces Human Naive Pluripotency
AU - Qin, Han
AU - Hejna, Miroslav
AU - Liu, Yanxia
AU - Percharde, Michelle
AU - Wossidlo, Mark
AU - Blouin, Laure
AU - Durruthy-Durruthy, Jens
AU - Wong, Priscilla
AU - Qi, Zhongxia
AU - Yu, Jingwei
AU - Qi, Lei S.
AU - Sebastiano, Vittorio
AU - Song, Jun S.
AU - Ramalho-Santos, Miguel
N1 - Funding Information:
We are grateful to Robert Blelloch, Marco Conti, and Susan Fisher for input during the course of this work; to Alex Dunn for antibodies and discussions; and to members of the M.R.-S. lab for discussions and critical reading of the manuscript. We thank Rudolf Jaenisch for the OCT4-ΔPE-GFP WIBR3 human ESCs, Fong Ming Koh for providing the pGAMA vector, and Kathryn Blaschke and Yuki Ohi for initial cloning of the YAP cDNA. This work was partially supported by a Siebel Stem Cells Institute Scholarship and a Stinehart Reed Seed Grant to V.S., NIH R01 CA163336 to J.S.S., and CIRM grant RB4-06028 and NIH R01 OD012204 to M.R.-S.
Funding Information:
We are grateful to Robert Blelloch, Marco Conti, and Susan Fisher for input during the course of this work; to Alex Dunn for antibodies and discussions; and to members of the M.R.-S. lab for discussions and critical reading of the manuscript. We thank Rudolf Jaenisch for the OCT4-ΔPE-GFP WIBR3 human ESCs, Fong Ming Koh for providing the pGAMA vector, and Kathryn Blaschke and Yuki Ohi for initial cloning of the YAP cDNA. This work was partially supported by a Siebel Stem Cells Institute Scholarship and a Stinehart Reed Seed Grant to V.S., NIH R01 CA163336 to J.S.S., and CIRM grant RB4-06028 and NIH R01 OD012204 to M.R.-S.
Publisher Copyright:
© 2016 The Authors.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/3/15
Y1 - 2016/3/15
N2 - 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.
AB - 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.
KW - Embryonic stem cells (ESCs)
KW - Hippo pathway
KW - Induced pluripotent stem cells (iPSCs)
KW - Lysophosphatidic acid (LPA)
KW - Naive pluripotency
KW - Pluripotent stem cells (PSCs)
KW - Yes-associated protein (YAP)
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UR - http://www.scopus.com/inward/citedby.url?scp=84960459407&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2016.02.036
DO - 10.1016/j.celrep.2016.02.036
M3 - Article
C2 - 26947063
AN - SCOPUS:84960459407
VL - 14
SP - 2301
EP - 2312
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 10
ER -