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YAP Induces Human Naive Pluripotency.

Han Qin1, Miroslav Hejna2, Yanxia Liu3

  • 1Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Departments of Ob/Gyn and Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; Center for Reproductive Sciences and Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.

Cell Reports
|March 8, 2016
PubMed
Summary

Scientists discovered that YAP, a Hippo pathway protein, is crucial for maintaining human naive pluripotent stem cells (PSCs). Overexpressing YAP or using LPA helps generate these valuable PSCs in vitro for developmental biology research.

Keywords:
Hippo pathwayYes-associated protein (YAP)embryonic stem cells (ESCs)induced pluripotent stem cells (iPSCs)lysophosphatidic acid (LPA)naive pluripotencypluripotent stem cells (PSCs)

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Area of Science:

  • Stem cell biology
  • Developmental biology
  • Cell signaling

Background:

  • Capturing and sustaining the human naive pluripotent stem cell (PSC) state in vitro is challenging.
  • The naive PSC state mirrors the pre-implantation embryonic stage.

Purpose of the Study:

  • To investigate the role of the Hippo pathway effector YAP in establishing the human naive PSC state.
  • To identify methods for generating and sustaining naive PSCs in vitro.

Main Methods:

  • Analyzing YAP localization in human blastocysts.
  • Overexpressing YAP in human embryonic stem cells (ESCs) and induced PSCs (iPSCs).
  • Utilizing lysophosphatidic acid (LPA) as a substitute for YAP.
  • Generating YAP knockout cells using CRISPR/Cas9.

Main Results:

  • Nuclear localization of YAP observed in the inner cell mass of human blastocysts.
  • YAP overexpression or LPA treatment promoted the generation of naive PSCs.
  • YAP/LPA-induced naive PSCs exhibited rapid growth, normal karyotype, teratoma formation, and transcriptional similarity to early embryos.
  • YAP/LPA suppressed GSK3 inhibition's differentiation effects.
  • YAP knockout cells showed impaired colony formation under naive conditions.

Conclusions:

  • YAP plays a critical, previously unrecognized role in the human naive PSC state.
  • YAP and LPA are key regulators for generating and maintaining human naive PSCs in vitro.
  • These findings have significant implications for understanding early human embryology and stem cell applications.