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GATA6 Plays an Important Role in the Induction of Human Definitive Endoderm, Development of the Pancreas, and Functionality of Pancreatic β Cells.

Abstract：

:Induced pluripotent stem cells were created from a pancreas agenesis patient with a mutation in GATA6. Using genome-editing technology, additional stem cell lines with mutations in both GATA6 alleles were generated and demonstrated a severe block in definitive endoderm induction, which could be rescued by re-expression of several different GATA family members. Using the endodermal progenitor stem cell culture system to bypass the developmental block at the endoderm stage, cell lines with mutations in one or both GATA6 alleles could be differentiated into β-like cells but with reduced efficiency. Use of suboptimal doses of retinoic acid during pancreas specification revealed a more severe phenotype, more closely mimicking the patient's disease. GATA6 mutant β-like cells fail to secrete insulin upon glucose stimulation and demonstrate defective insulin processing. These data show that GATA6 plays a critical role in endoderm and pancreas specification and β-like cell functionality in humans.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Tiyaboonchai A,Cardenas-Diaz FL,Ying L,Maguire JA,Sim X,Jobaliya C,Gagne AL,Kishore S,Stanescu DE,Hughes N,De Leon DD,French DL,Gadue P

doi

10.1016/j.stemcr.2016.12.026

subject

Has Abstract

pub_date

2017-03-14 00:00:00

pages

589-604

issue

3

issn

2213-6711

pii

S2213-6711(16)30316-2

journal_volume

8

pub_type

杂志文章

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