A miR‐372/let‐7 Axis Regulates Human Germ Versus Somatic Cell Fates
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 huma...
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Published in | Stem cells (Dayton, Ohio) Vol. 34; no. 7; pp. 1985 - 1991 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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United States
Oxford University Press
01.07.2016
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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
Let‐7 and miR‐294 antagonistically regulate somatic versus germline fates through their influence on multiple cellular pathways. |
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AbstractList | 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. 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. 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. 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. The embryonic stem cell cycle (ESCC) and let-7 families of miRNAs function antagonistically in the switch between mouse embryonic stem cell (mESC) 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 while let-7 antagonizes PGCLC differentiation. Knockdown of the individual miR-372 targets SMARCC1 , MECP2 , CDKN1 , RBL2 , RHOC , and TGFBR2 increased PGCLC production, while knockdown of the let-7 targets CMYC and NMYC suppressed PGCLC differentiation. These findings uncover a miR-372/let-7 axis common to induced pluripotency and primordial germ cell (PGC) specification. Let-7 and miR-294 antagonistically regulate somatic versus germline fates through their influence on multiple cellular pathways. 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 |
Author | Kissner, Michael Tran, Nam D. Blelloch, Robert H. Subramanyam, Deepa Parchem, Ronald J. Laird, Diana J. |
AuthorAffiliation | 1 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, CA. USA |
AuthorAffiliation_xml | – name: 1 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, CA. USA |
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Snippet | 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... 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... Abstract The embryonic stem cell cycle (ESCC) and let-7 families of miRNAs function antagonistically in the switch between mouse embryonic stem cell... The embryonic stem cell cycle (ESCC) and let-7 families of miRNAs function antagonistically in the switch between mouse embryonic stem cell (mESC) self-renewal... |
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SubjectTerms | 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 |
Title | A miR‐372/let‐7 Axis Regulates Human Germ Versus Somatic Cell Fates |
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