DICER1 is essential for self-renewal of human embryonic stem cells Journal Article

Authors: Teijeiro, V.; Yang, D.; Majumdar, S.; González, F.; Rickert, R. W.; Xu, C.; Koche, R.; Verma, N.; Lai, E. C.; Huangfu, D.
Article Title: DICER1 is essential for self-renewal of human embryonic stem cells
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. Huangfu and colleagues report an unexpected requirement for DICER1 in preventing death-receptor-mediated apoptosis in hESCs. This essential pro-survival role is largely mediated by mir-302-367 and mir-371-373 cluster members that bear the seed sequence “AAGUGC” shared by the ESC-specific cell-cycle-regulating family of miRNAs. This work provides a robust platform for interrogating miRNA function in hESC pluripotency and differentiation. © 2018 The Authors
Keywords: apoptosis; self-renewal; dicer1; human pluripotent stem cells (hpscs); human embryonic stem cells (hescs); escc mirnas; micrornas (mirnas)
Journal Title: Stem Cell Reports
Volume: 11
Issue: 3
ISSN: 2213-6711
Publisher: Cell Press  
Date Published: 2018-09-11
Start Page: 616
End Page: 625
Language: English
DOI: 10.1016/j.stemcr.2018.07.013
PROVIDER: scopus
PMCID: PMC6135725
PUBMED: 30146489
Notes: Article -- Export Date: 1 November 2018 -- Source: Scopus
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MSK Authors
  1. Eric C Lai
    117 Lai
  2. Danwei Huangfu
    28 Huangfu
  3. Nipun Verma
    9 Verma
  4. Richard Patrick Koche
    52 Koche
  5. Dapeng Yang
    2 Yang
  6. Chunlong Xu
    1 Xu