Regulation of self-renewal activity of spermatogonial stem cells

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  • 精子幹細胞の自己複製と維持のメカニズムの解明
  • セイシ カンサイボウ ノ ジコ フクセイ ト イジ ノ メカニズム ノ カイメイ

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Abstract

<p>Spermatogonial stem cell (SSCs) are the sources of sperm throughout adult life. Though the number of SSCs in testes is limited, they are maintained by self-renewal division. To investigate the life span of SSCs in vivo, we specifically marked SSCs of mouse testes by virus infection, and found that offspring were born from identical SSCs after >482 days. The result suggests that single SSCs can contribute to sperm production with a remarkably long life-span. We established a culture system to expand SSCs in vitro, and showed that SSCs maintain genetic and epigenetic properties after 2 year’s culture, and produced normal offspring after transplantation into testes. Using this culture system, we identified several signaling molecules involved in SSC self-renewal division. Those include GDNF and FGF2, the cytokines, both of which play important roles in SSC culture, and their downstream signaling molecules, cell cycle regulators, and glycolytic pathway. Technique to manipulate SSCs will be useful for male infertility treatment and animal transgenesis, and the knowledge of SSC self-renewal mechanism will help establishing a method to expand SSCs of a wide range of animals in vitro.</p>

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