GATA6 is essential for endoderm formation from human pluripotent stem cells. Biol Open 2017 Jul 15;6(7):1084-1095
Date
06/14/2017Pubmed ID
28606935Pubmed Central ID
PMC5550920DOI
10.1242/bio.026120Scopus ID
2-s2.0-85024118986 (requires institutional sign-in at Scopus site) 45 CitationsAbstract
Protocols have been established that direct differentiation of human pluripotent stem cells into a variety of cell types, including the endoderm and its derivatives. This model of differentiation has been useful for investigating the molecular mechanisms that guide human developmental processes. Using a directed differentiation protocol combined with shRNA depletion we sought to understand the role of GATA6 in regulating the earliest switch from pluripotency to definitive endoderm. We reveal that GATA6 depletion during endoderm formation results in apoptosis of nascent endoderm cells, concomitant with a loss of endoderm gene expression. We show by chromatin immunoprecipitation followed by DNA sequencing that GATA6 directly binds to several genes encoding transcription factors that are necessary for endoderm differentiation. Our data support the view that GATA6 is a central regulator of the formation of human definitive endoderm from pluripotent stem cells by directly controlling endoderm gene expression.
