2006 Fiscal Year Final Research Report Summary
Mechanisms regulating mouse germline establishment and stem cell systems
| Project/Area Number |
17590344
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Osaka University |
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Principal Investigator |
KIMURA Tohru Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50280962)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Toru Osaka University, Graduate School of Frontier Biosciences, Professor, 生命機能研究所, 教授 (00172370)
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| Project Period (FY) |
2005 – 2006
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| Keywords | primordial germ ce;; / ES cell / EG cell / stem cell system / PI3K / Akt signal / Wnt / β-catenin signal |
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| Research Abstract |
Promordial germ cells (PGC) are embryonic germ cell precursors PGC dedifferentiate to pluripotent stem cells called embryonic germ (EG) cells, which have the pluripotent differentiation capacities similar to embryonic stem (ES) cells. In this study, we have analyzed the roles of Wnt/β-catenin and Akt signals in the development al capacities of PGCs. Furthermore, we investigated the effects of Akr activation in mouse tissue stem cell systems.
1. Role of Wnt/β-catenin signal in mouse PGC development
We have generated the transgenic mice which express stabilized mutant form of β-catenin from endogenous locus in PGC. The mice did not develop testicular teratomas, but instead showed germ cell deficiency. Instead, the germ cell deficiency resulted from aberrant cell cycle progression, indicating that inhibition of Wnt/β-catenin signaling is essential for PGC proliferation
2. Effects of Akt signaling activation in EG cell production
Previously, we have shown that PGC-specific PTEN knockout mice developed testicular teratomas and showed increased rates of RG cell formation. These results revealed that enhancement of PI3K signaling induced dedifferentiation of PGCs to pluripotent stem cells. To examine the downstream of PI3K, we have generated the transgenic mice that expressed Akt-Mer fusion protein. Using this transgenic system, we have demonstrated that Akt activation downstream of PI3K promotes the EG cell production.
3. Effects od Akt activation in tissue stem cell systems
We chose the epidermal stem cells as the model of tissue stem cells to examine the effects of Akt signaling activation. We used the above-mentioned Akt-Mer transgenic mice and revealed that Akt activation in epidermal stem cell systems leads to activation of quiescent stem cells and subsequent production and expansion of progenitors.
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