A miR‐372/let‐7 Axis Regulates Human Germ Versus Somatic Cell Fates

• Published in: Stem cells (Dayton, Ohio) Vol. 34; no. 7; pp. 1985 - 1991
• Main Authors: Tran, Nam D., Kissner, Michael, Subramanyam, Deepa, Parchem, Ronald J., Laird, Diana J., Blelloch, Robert H.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.07.2016
• Subjects: Biomarkers - metabolism; Cell cycle; Cell Lineage; Cell self-renewal; Differentiation; Embryo cells; Embryonic stem cells; Embryos; Germ Cells - cytology; Germ Cells - metabolism; Humans; let‐7; MeCP2 protein; Methyl-CpG binding protein; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; mir‐372; Pluripotency; Primordial germ cells; Signal Transduction - genetics; Somatic cells; Sponges; Stem cell transplantation; Stem cells; mir-372; microRNA; Primordial germ cells; let-7; Embryonic stem cells
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.2378

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 Cells 2016;34:1985–1991 Let‐7 and miR‐294 antagonistically regulate somatic versus germline fates through their influence on multiple cellular pathways.