Genetic Influences in Mouse Spermatogonial Stem Cell Self-Renewal

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  • KANATSU-SHINOHARA Mito
    Department of Molecular Genetics, Graduate School of Medicine, Kyoto University
  • OGONUKI Narumi
    The Institute for Physical and Chemical Research (RIKEN), Bioresource Center
  • MIKI Hiromi
    The Institute for Physical and Chemical Research (RIKEN), Bioresource Center
  • INOUE Kimiko
    The Institute for Physical and Chemical Research (RIKEN), Bioresource Center
  • MORIMOTO Hiroko
    Department of Molecular Genetics, Graduate School of Medicine, Kyoto University
  • TAKASHIMA Seiji
    Department of Molecular Genetics, Graduate School of Medicine, Kyoto University
  • OGURA Atsuo
    The Institute for Physical and Chemical Research (RIKEN), Bioresource Center
  • SHINOHARA Takashi
    Department of Molecular Genetics, Graduate School of Medicine, Kyoto University Japan Science and Technology Agency, CREST

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Spermatogonial stem cells (SSCs) are slowly dividing cells that undergo self-renewal division to support spermatogenesis. Although the effects of genetic background in stem cell self-renewal have been well studied in hematopoietic stem cells, little is known about its effect on stem cells in other self-renewing tissues, including SSCs. To examine whether genetic factors are involved in regulation of SSC self-renewal, we first studied spermatogenesis in different inbred mouse strains (C57BL/6, DBA/2, AKR, BALB/C and C3H) after chemical damage caused by busulfan. Spermatogenesis in the DBA/2 and AKR strains was relatively resistant to busulfan treatment, whereas spermatogenesis was diminished in C57BL/6 mice and nearly ablated in C3H and BALB/C mice. Serial germ cell transplantation experiments provided functional evidence that SSCs with the DBA/2 background expanded more rapidly than those with the B6 background. Finally, we also employed the Germline Stem (GS) cell culture technique to examine the self-renewal activity in vitro. Although genetic manipulation of GS cells has been limited to those from the DBA/2 background, we produced transgenic offspring of the C3H background by electroporation of GS cells with a plasmid vector. Our results underscore the importance of genetic factors in SSC self-renewal. Furthermore, application of genetic modification techniques to GS cells with non-DBA/2 backgrounds extends the potential of a SSC-based approach in male germline modification.<br>

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