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DICER1 对于人类胚胎干细胞的自我更新至关重要。

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

机构信息

Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, 1300 York Avenue, New York, NY 10065, USA.

Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

出版信息

Stem Cell Reports. 2018 Sep 11;11(3):616-625. doi: 10.1016/j.stemcr.2018.07.013. Epub 2018 Aug 23.

DOI:10.1016/j.stemcr.2018.07.013
PMID:30146489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6135725/
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.

摘要

微小 RNA（miRNA）是一种保守的基因沉默系统的效应物，在转录后调控中具有广泛的作用。由于功能上的重叠，为单个 miRNA 分配特定的功能一直具有挑战性。DICER1 将 pre-miRNA 发夹切割成成熟的 miRNA，先前已经生成了 Dicer1 敲除的小鼠胚胎干细胞，以研究 miRNA 在早期小鼠发育中的功能。在这里，我们报告了 DICER1 对人类胚胎干细胞（hESC）自我更新的必需性。利用条件性敲除方法，我们发现 DICER1 的缺失导致死亡受体介导的凋亡增加和 hESC 自我更新失败。我们进一步设计了靶向 miRNA 筛选策略，并发现了 mir-302-367 和 mir-371-373 簇成员的重要生存促进作用，这些簇带有 AAGUGC 种子序列。该平台非常适合剖析单个 miRNA 在 hESC 自我更新和分化中的作用，这可能有助于我们更好地理解人类胚胎的早期发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/e705cf5375a3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/71de0610bea3/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/f9af51b07e86/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/326326acc9ff/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/7e782f1571a2/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/e705cf5375a3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/71de0610bea3/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/f9af51b07e86/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/326326acc9ff/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/7e782f1571a2/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf73/6135725/e705cf5375a3/gr4.jpg

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