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SIX2 Regulates Human β Cell Differentiation from Stem Cells and Functional Maturation In Vitro.

Abstract：

:Generation of insulin-secreting β cells in vitro is a promising approach for diabetes cell therapy. Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are differentiated to β cells (SC-β cells) and mature to undergo glucose-stimulated insulin secretion, but molecular regulation of this defining β cell phenotype is unknown. Here, we show that maturation of SC-β cells is regulated by the transcription factor SIX2. Knockdown (KD) or knockout (KO) of SIX2 in SC-β cells drastically limits glucose-stimulated insulin secretion in both static and dynamic assays, along with the upstream processes of cytoplasmic calcium flux and mitochondrial respiration. Furthermore, SIX2 regulates the expression of genes associated with these key β cell processes, and its expression is restricted to endocrine cells. Our results demonstrate that expression of SIX2 influences the generation of human SC-β cells in vitro.

journal_name

Cell Rep

journal_title

Cell reports

authors

Velazco-Cruz L,Goedegebuure MM,Maxwell KG,Augsornworawat P,Hogrebe NJ,Millman JR

doi

10.1016/j.celrep.2020.107687

subject

Has Abstract

pub_date

2020-05-26 00:00:00

pages

107687

issue

8

issn

2211-1247

pii

S2211-1247(20)30640-9

journal_volume

31

pub_type

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