Genome Editing of Lineage Determinants in Human Pluripotent Stem Cells Reveals Mechanisms of Pancreatic Development and Diabetes.
作者： Zengrong Zhu , Qing V. Li , Kihyun Lee , Bess P. Rosen , Federico González
DOI: 10.1016/J.STEM.2016.03.015
关键词:
摘要: Directed differentiation of human pluripotent stem cells (hPSCs) into somatic counterparts is a valuable tool for studying disease. However, examination developmental mechanisms in hPSCs remains challenging given complex multi-factorial actions at different stages. Here, we used TALEN and CRISPR/Cas-mediated gene editing hPSC-directed systematic analysis the roles eight pancreatic transcription factors (PDX1, RFX6, PTF1A, GLIS3, MNX1, NGN3, HES1, ARX). Our not only verified conserved requirements between mice humans but also revealed number previously unsuspected with implications type 2 diabetes. These include role RFX6 regulating progenitors, haploinsufficient requirement PDX1 β cell differentiation, potentially divergent NGN3 mice. findings support use genome as strategy understanding underlying congenital disorders.
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