Lin28a Regulates Germ Cell Pool Size and Fertility§

Authors

  • Gen Shinoda,

    1. Stem Cell Transplantation Program, Stem Cell Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA
    2. Harvard Stem Cell Institute, Boston, Massachusetts, USA
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  • T. Yvanka De Soysa,

    1. Stem Cell Transplantation Program, Stem Cell Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA
    2. Harvard Stem Cell Institute, Boston, Massachusetts, USA
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  • Marc T. Seligson,

    1. Harvard Stem Cell Institute, Boston, Massachusetts, USA
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  • Akiko Yabuuchi,

    1. Stem Cell Transplantation Program, Stem Cell Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA
    2. Harvard Stem Cell Institute, Boston, Massachusetts, USA
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  • Yuko Fujiwara,

    1. Stem Cell Transplantation Program, Stem Cell Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA
    2. Harvard Stem Cell Institute, Boston, Massachusetts, USA
    3. Howard Hughes Medical Institute, Boston, Massachusetts, USA
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  • Pei Yi Huang,

    1. Stem Cell Transplantation Program, Stem Cell Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA
    2. Program in Cellular and Molecular Medicine, Boston Children's Hospital, Immune Disease Institute, Boston, Massachusetts, USA
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  • John P. Hagan,

    1. Stem Cell Transplantation Program, Stem Cell Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA
    2. Harvard Stem Cell Institute, Boston, Massachusetts, USA
    3. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    4. Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, Ohio, USA
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  • Richard I. Gregory,

    1. Stem Cell Transplantation Program, Stem Cell Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA
    2. Harvard Stem Cell Institute, Boston, Massachusetts, USA
    3. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
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  • Eric G. Moss,

    1. Department of Molecular Biology, The University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA
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  • George Q. Daley

    Corresponding author
    1. Stem Cell Transplantation Program, Stem Cell Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA
    2. Harvard Stem Cell Institute, Boston, Massachusetts, USA
    3. Howard Hughes Medical Institute, Boston, Massachusetts, USA
    4. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    5. Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, USA
    6. Manton Center for Orphan Disease Research, Boston, Massachusetts, USA
    • Children's Hospital Boston, One Blackfan circle, Karp Building, 7th Floor, Boston, Massachusetts 02115, USA
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    • Telephone: 617-919-2013; Fax: 617-730-0222


  • Author contributions: G.S.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; T.Y.S. and M.T.S.: collection and/or assembly of data; A.Y., J.P.H., and R.I.G.: provision of study materials; Y.F. and P.Y.H.: collection and/or assembly of data, and data analysis and interpretation; E.G.M.: provision of study material or patients. G.Q.D.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS February 4, 2013.

Abstract

Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males, the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild-type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. STEM CELLS 2013;31:1001–1009

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