Journal
STEM CELL REPORTS
Volume 11, Issue 3, Pages 616-625Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2018.07.013
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Funding
- MSKCC Functional Genomics Initiative
- NIH/NIDDK [R01DK096239]
- MSKCC Cancer Center support grant [P30CA008748]
- NIH [T32HD060600]
- R01 Supplement grant [3R01DK096239-03S1]
- NIH/NIGMS [R01-GM083300]
- NIH/NHLBI [R01-HL135564]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [T32HD060600] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [P30CA008748] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL135564] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK096239] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM083300] Funding Source: NIH RePORTER
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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.
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