DICER1 Is Essential for Self-Renewal of Human Embryonic Stem Cells

Stem Cell Reports
Virginia TeijeiroDanwei Huangfu

Abstract

MicroRNAs (miRNAs) are the effectors of a conserved gene-silencing system with broad roles in post-transcriptional regulation. Due to functional overlaps, assigning specific functions to individual miRNAs has been challenging. DICER1 cleaves pre-miRNA hairpins into mature miRNAs, and previously Dicer1 knockout mouse embryonic stem cells have been generated to study miRNA function in early mouse development. Here we report an essential requirement of DICER1 for the self-renewal of human embryonic stem cells (hESCs). Utilizing a conditional knockout approach, we found that DICER1 deletion led to increased death receptor-mediated apoptosis and failure of hESC self-renewal. We further devised a targeted miRNA screening strategy and uncovered essential pro-survival roles of members of the mir-302-367 and mir-371-373 clusters that bear the seed sequence AAGUGC. This platform is uniquely suitable for dissecting the roles of individual miRNAs in hESC self-renewal and differentiation, which may help us better understand the early development of human embryos.

Citations

Aug 14, 2019·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Qing V LiDanwei Huangfu
Jul 28, 2019·International Journal of Molecular Sciences·Zhenwu ZhangChao-Po Lin
Sep 4, 2020·International Journal of Molecular Sciences·Giuseppina DivisatoSilvia Parisi
Dec 3, 2020·International Journal of Molecular Sciences·Indrek TeinoToivo Maimets
Apr 11, 2021·Cancer Treatment and Research Communications·Ju-Yoon YoonMarjan Rouzbahman

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Methods Mentioned

BETA
transgenic
Knockout
flow-cytometry
flow cytometry
RNA-seq
transfection

Software Mentioned

CARMAweb
MirTarget
GraphPad Prism
TargetScan
R
clusterProfiler

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