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Biol Open. 2017 Jul 15;6(7):1084-1095. doi: 10.1242/bio.026120.

GATA6 is essential for endoderm formation from human pluripotent stem cells.

Author information

1
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
2
Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
3
Division of Pediatric Hematology, Oncology, and Blood and Marrow Transplant, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
4
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA duncanst@musc.edu.
5
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.

Abstract

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.

KEYWORDS:

Endoderm development; GATA; Pluripotent stem cell differentiation; Transcriptional control

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