2010 Fiscal Year Final Research Report
Self-renewal mechanism of spermatogonial stem cells
| Project/Area Number |
19689007
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
SHINOHARA Mito Kyoto University, 医学研究科, 助教 (10372591)
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| Project Period (FY) |
2007 – 2010
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| Keywords | 幹細胞 / 生殖 / 遺伝学 |
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| Research Abstract |
Spermatogonial stem cells (SSCs) in testes are the foundation of spermatogenesis throughout adult life. In 2003, we established a long-term in vitro culture system of mouse SSCs, and designated the cultured cells as Germline stem (GS) cells. GS cells constantly proliferate for a long-term period and expand for 10^<85>-fold (139 passages)during 2 years culture, without losing stem cell activity, normal imprinting patterns, and normal karyotype. Current research was oriented to elucidate the limitation of SSC stability, and the mechanism underlying a stability self-renewal system of SSCs, and how the breakdown of safety mechanism occurs.
First, we continued to culture GS cells beyond 2 years, and examined their life-span, and observed the effects of a long-term culture. We found that GS cells continue to proliferate for >5 years, without losing normal karyotype, but their stem cell activity and differentiation potential became gradually limited by a long-term culture.
Second, we investigated the signaling pathways regulating SSC self-renewal, and found that the signal from Glial cell line derived neurotrophic factor (GDNF), the self-renewal factor of SSCs, is transduced through Akt/PI3K pathway, and that Ras/Cyclin D2 pathway is also involved in self-renewal of SSCs. In addition, we found that p21 and p27,Cyclin-dependent kinase inhibitor (CDKI)are involved in self-renewal and differentiation of SSCs.
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[Journal Article] Abnormal DNA methyltransferase expression in mouse germline stem cells results in spermatogenic defects.2009
Author(s)
Takashima S., Takehashi M., Lee J., Chuma S., Okano M., Hata K., Suetake I., Nakatsuji N., Miyoshi H., Tajima S., Tanaka Y., Toyokuni S., Sasaki H., Kanatsu-Shinohara M., Shinohara T.
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Journal Title
Biol.Reprod. 81(1)
Pages: 64-155
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[Journal Article] Production of knockout mice by gene targeting in multipotent germline stem cells.2007
Author(s)
Takehashi M, Kanatsu-Shinohara M, Miki H, Lee J, Kazuki Y, Inoue K, Ogonuki N, Toyokuni S, Oshimura M, Ogura A, Shinohara, T.
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Journal Title
Dev.Biol. 312
Pages: 52-344
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