title: A miR-372/let-7 Axis Regulates Human Germ Versus Somatic Cell Fates.
abstract: 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.
authors.affiliation: Departments of OB/Gyn and Urology, Center for Reproductive Sciences, and the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Nam D
authors.initials: ND
authors.lastname: Tran
authors.affiliation: Departments of OB/Gyn and Urology, Center for Reproductive Sciences, and the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kissner
authors.affiliation: Departments of OB/Gyn and Urology, Center for Reproductive Sciences, and the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Subramanyam
authors.affiliation: Departments of OB/Gyn and Urology, Center for Reproductive Sciences, and the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Parchem
authors.affiliation: Departments of OB/Gyn and Urology, Center for Reproductive Sciences, and the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Laird
authors.affiliation: Departments of OB/Gyn and Urology, Center for Reproductive Sciences, and the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Blelloch
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D015415:Biomarkers; C561021:MIRN372 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
keywords: Embryonic stem cells; Primordial germ cells; let-7; microRNA; mir-372