Specifying the Anterior Primitive Streak by Modulating YAP1 Levels in Human Pluripotent Stem Cells

Hui Ting Hsu, Conchi Estarás, Ling Huang, Katherine A. Jones

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Specifying the primitive streak (PS) guides stem cell differentiation in vitro; however, much remains to be learned about the transcription networks that direct anterior and posterior PS cells (APS and PPS, respectively) to differentiate to distinct mesendodermal subpopulations. Here, we show that APS genes are predominantly induced in YAP1 −/− human embryonic stem cells (hESCs) in response to ACTIVIN. This finding establishes the Hippo effector YAP1 as a master regulator of PS specification, functioning to repress ACTIVIN-regulated APS genes in hESCs. Moreover, transient exposure of wild-type hESCs to dasatinib, a potent C-SRC/YAP1 inhibitor, enables differentiation to APS-derived endoderm and cardiac mesoderm in response to ACTIVIN. Importantly, these cells can differentiate efficiently to normal beating cardiomyocytes without the cytoskeletal defect seen in YAP1 −/− hESC-derived cardiomyocytes. Overall, we uncovered an induction mechanism to generate APS cells using a cocktail of ACTIVIN and YAP1i molecules that holds practical implications for hESC and induced pluripotent stem cell differentiation into distinct mesendodermal lineages.

Original languageEnglish
Pages (from-to)1357-1364
Number of pages8
JournalStem Cell Reports
Volume11
Issue number6
DOIs
StatePublished - Dec 11 2018
Externally publishedYes

Keywords

  • ACTIVIN
  • YAP
  • cardiomyocyte differentiation
  • human embryonic stem cells
  • iPSC
  • primitive streak

Fingerprint

Dive into the research topics of 'Specifying the Anterior Primitive Streak by Modulating YAP1 Levels in Human Pluripotent Stem Cells'. Together they form a unique fingerprint.

Cite this