YAP Induces Human Naive Pluripotency

Han Qin; Miroslav Hejna; Yanxia Liu; Michelle Percharde; Mark Wossidlo; Laure Blouin; Jens Durruthy-Durruthy; Priscilla Wong; Zhongxia Qi; Jingwei Yu; Lei S. Qi; Vittorio Sebastiano; Jun S. Song; Miguel Ramalho-Santos

doi:10.1016/j.celrep.2016.02.036

Cell Reports (Mar 2016)

YAP Induces Human Naive Pluripotency

Han Qin,
Miroslav Hejna,
Yanxia Liu,
Michelle Percharde,
Mark Wossidlo,
Laure Blouin,
Jens Durruthy-Durruthy,
Priscilla Wong,
Zhongxia Qi,
Jingwei Yu,
Lei S. Qi,
Vittorio Sebastiano,
Jun S. Song,
Miguel Ramalho-Santos

Affiliations

Han Qin: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
Miroslav Hejna: Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA
Yanxia Liu: Departments of Bioengineering and Chemical and Systems Biology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA
Michelle Percharde: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
Mark Wossidlo: Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA
Laure Blouin: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
Jens Durruthy-Durruthy: Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA
Priscilla Wong: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
Zhongxia Qi: Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Jingwei Yu: Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Lei S. Qi: Departments of Bioengineering and Chemical and Systems Biology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA
Vittorio Sebastiano: Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA
Jun S. Song: Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA
Miguel Ramalho-Santos: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA

DOI: https://doi.org/10.1016/j.celrep.2016.02.036
Journal volume & issue: Vol. 14, no. 10
pp. 2301 – 2312

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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