Journal
STEM CELLS
Volume 34, Issue 7, Pages 1985-1991Publisher
WILEY
DOI: 10.1002/stem.2378
Keywords
Embryonic stem cells; Primordial germ cells; microRNA; mir-372; let-7
Categories
Funding
- California Institute Regeneration Medicine (CIRM) Fellowship [TG2-01153]
- Weston Havens Foundation
- CIRM New Faculty Award [RN-00906]
- NIH [R01 NS057221, DP2 OD007420]
- NIGMS [R01 GM101180]
- NICHD [U54 HD055764]
- NIEHS [R21 ES023297]
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The embryonic stem cell cycle (ESCC) and let-7 families of miRNAs function antagonistically in the switch between mouse embryonic stem cell self-renewal and somatic differentiation. Here, we report that the human ESCC miRNA miR-372 and let-7 act antagonistically in germline differentiation from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs). hESC and iPSC-derived primordial germ cell-like cells (PGCLCs) expressed high levels of miR-372 and conversely, somatic cells expressed high levels of let-7. Manipulation of miRNA levels by introduction of miRNA mimics or knockdown with miRNA sponges demonstrated that miR-372 promotes whereas let-7 antagonizes PGCLC differentiation. Knockdown of the individual miR-372 targets SMARCC1, MECP2, CDKN1, RBL2, RHOC, and TGFBR2 increased PGCLC production, whereas knockdown of the let-7 targets CMYC and NMYC suppressed PGCLC differentiation. These findings uncover a miR-372/let-7 axis regulating human primordial germ cell (PGC) specification. Stem Cells2016;34:1985-1991
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