Conversion of embryonic stem cells into extraembryonic lineages by CRISPR-mediated activators

通过 CRISPR 介导的激活剂将胚胎干细胞转化为胚外谱系

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作者:Shu Wei, Qingjian Zou, Sisi Lai, Quanjun Zhang, Li Li, Quanmei Yan, Xiaoqing Zhou, Huilin Zhong, Liangxue Lai

Abstract

The recently emerged CRISPR/Cas9 technique has opened a new perspective on readily editing specific genes. When combined with transcription activators, it can precisely manipulate endogenous gene expression. Here, we enhanced the expression of endogenous Cdx2 and Gata6 genes by CRISPR-mediated activators, thus mouse embryonic stem cells (ESCs) were directly converted into two extraembryonic lineages, i.e., typical trophoblast stem cells (TSCs) and extraembryonic endoderm cells (XENCs), which exhibited characters of TSC or XENC derived from the blastocyst extraembryonic lineages such as cell morphology, specific gene expression, and differentiation ability in vitro and in vivo. This study demonstrates that the cell fate can be effectively manipulated by directly activating of specific endogenous gene expression with CRISPR-mediated activator.

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