Title | DICER1 Is Essential for Self-Renewal of Human Embryonic Stem Cells. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Teijeiro V, Yang D, Majumdar S, González F, Rickert RW, Xu C, Koche R, Verma N, Lai EC, Huangfu D |
Journal | Stem Cell Reports |
Volume | 11 |
Issue | 3 |
Pagination | 616-625 |
Date Published | 2018 09 11 |
ISSN | 2213-6711 |
Keywords | Apoptosis, Base Sequence, Cell Line, Cell Self Renewal, DEAD-box RNA Helicases, Gene Deletion, Gene Expression Regulation, Gene Knockout Techniques, Human Embryonic Stem Cells, Humans, MicroRNAs, Ribonuclease III |
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. |
DOI | 10.1016/j.stemcr.2018.07.013 |
Alternate Journal | Stem Cell Reports |
PubMed ID | 30146489 |
PubMed Central ID | PMC6135725 |
Grant List | R01 HL135564 / HL / NHLBI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States T32 HD060600 / HD / NICHD NIH HHS / United States R01 GM083300 / GM / NIGMS NIH HHS / United States R01 DK096239 / DK / NIDDK NIH HHS / United States |
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