YAP Induces Human Naive Pluripotency

被引：167

作者：

Qin, Han ^{[1
,2
,3
,4
,5
,17
]}

Hejna, Miroslav ^{[6
,7
,8
]}

Liu, Yanxia ^{[9
,10
,11
,12
]}

Percharde, Michelle ^{[1
,2
,3
,4
,5
]}

Wossidlo, Mark ^{[13
,14
,15
]}

Blouin, Laure ^{[1
,2
,3
,4
,5
]}

Durruthy-Durruthy, Jens ^{[13
,14
,15
]}

Wong, Priscilla ^{[1
,2
,3
,4
,5
]}

Qi, Zhongxia ^{[16
]}

Yu, Jingwei ^{[16
]}

Qi, Lei S. ^{[9
,10
,11
,12
]}

Sebastiano, Vittorio ^{[13
,14
,15
]}

Song, Jun S. ^{[6
,7
,8
]}

Ramalho-Santos, Miguel ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Ob Gyn, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Ctr Reprod Sci, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA

[6] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA

[7] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA

[8] Univ Illinois, Dept Phys, Urbana, IL 61801 USA

[9] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA

[10] Stanford Univ, Sch Med, Dept Chem, Stanford, CA 94305 USA

[11] Stanford Univ, Sch Med, Dept Syst Biol, Stanford, CA 94305 USA

[12] Stanford Univ, Sch Med, ChEM H, Stanford, CA 94305 USA

[13] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[14] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA

[15] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Stanford, CA 94305 USA

[16] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA

[17] Genentech Inc, San Francisco, CA 94080 USA

来源：

CELL REPORTS | 2016年 / 14卷 / 10期

关键词：

HIPPO SIGNALING PATHWAY; EMBRYONIC STEM-CELLS; SYSTEMATIC IDENTIFICATION; GROUND-STATE; INDUCTION; EXPRESSION; DERIVATION; CIRCUITRY; COMPLEX; CULTURE;

D O I：

10.1016/j.celrep.2016.02.036

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：2301 / 2312

页数：12

共 43 条

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YAP/TAZ Incorporation in the β-Catenin Destruction Complex Orchestrates the Wnt Response [J].