YAP Induces Human Naive Pluripotency
Copyright policy )YAP Induces Human Naive Pluripotency
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.
- University of California, San Francisco United States
- Reproductive Science Center United States
- Stanford University United States
- University of California United States
- University of Illinois System United States
Male, Pyridines, Hippo pathway, Medical Physiology, Regenerative Medicine, Yes-associated protein, Glycogen Synthase Kinase 3, Stem Cell Research - Nonembryonic - Human, Heterochromatin, 2.1 Biological and endogenous factors, Biology (General), Wnt Signaling Pathway, Cells, Cultured, Cultured, Teratoma, Adaptor Proteins, Cell Differentiation, Biological Sciences, embryonic stem cells, Yes-associated protein (YAP), lysophosphatidic acid (LPA), Biological sciences, embryonic stem cells (ESCs), Benzamides, RNA Interference, Female, pluripotent stem cells, Pluripotent Stem Cells, induced pluripotent stem cells, QH301-705.5, 1.1 Normal biological development and functioning, Cells, pluripotent stem cells (PSCs), Induced Pluripotent Stem Cells, Karyotype, 610, Article, Humans, Stem Cell Research - Embryonic - Human, Embryonic Stem Cells, Adaptor Proteins, Signal Transducing, Stem Cell Research - Induced Pluripotent Stem Cell, naive pluripotency, Signal Transducing, Diphenylamine, YAP-Signaling Proteins, Stem Cell Research, Phosphoproteins, Pyrimidines, Blastocyst, Gene Expression Regulation, induced pluripotent stem cells (iPSCs), Biochemistry and Cell Biology, CRISPR-Cas Systems, Lysophospholipids, lysophosphatidic acid, Transcription Factors
Male, Pyridines, Hippo pathway, Medical Physiology, Regenerative Medicine, Yes-associated protein, Glycogen Synthase Kinase 3, Stem Cell Research - Nonembryonic - Human, Heterochromatin, 2.1 Biological and endogenous factors, Biology (General), Wnt Signaling Pathway, Cells, Cultured, Cultured, Teratoma, Adaptor Proteins, Cell Differentiation, Biological Sciences, embryonic stem cells, Yes-associated protein (YAP), lysophosphatidic acid (LPA), Biological sciences, embryonic stem cells (ESCs), Benzamides, RNA Interference, Female, pluripotent stem cells, Pluripotent Stem Cells, induced pluripotent stem cells, QH301-705.5, 1.1 Normal biological development and functioning, Cells, pluripotent stem cells (PSCs), Induced Pluripotent Stem Cells, Karyotype, 610, Article, Humans, Stem Cell Research - Embryonic - Human, Embryonic Stem Cells, Adaptor Proteins, Signal Transducing, Stem Cell Research - Induced Pluripotent Stem Cell, naive pluripotency, Signal Transducing, Diphenylamine, YAP-Signaling Proteins, Stem Cell Research, Phosphoproteins, Pyrimidines, Blastocyst, Gene Expression Regulation, induced pluripotent stem cells (iPSCs), Biochemistry and Cell Biology, CRISPR-Cas Systems, Lysophospholipids, lysophosphatidic acid, Transcription Factors
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