| Project/Area Number |
15590343
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
KIMURA Tohru Osaka University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (50280962)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAKANO Toru Osaka University, Graduate School of Frontier Bioscience, Professor, 大学院・生命機能研究科, 教授 (00172370)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | primordial germ cell / ES cell / Wnt / β-catenin signal / PI3K / Akt signal / germ cell / stem cell / 幹細胞システム / P13キナーゼ / PTEN / germ cell-less |
|---|
| Research Abstract |
Promordial germ cells (PGC) are embryonic germ cell precursors. PGC dedifferentiate to pluripotent stem cells called embryonic germ (EG) cells, that have the similar differentiation capacities to embryonic stem (ES) cells. In this study, we have analyzed the roles of Wnt/β-catenin signal and PI3K (phosphoinositide-3 kinase)/Akt signal in PGC development and differentiation capacities of ES cells.
(1) Role of Wnt/β-catenin signal in mouse PGC development
Expression of canonical Wnt molecules was low in tastes and ovaries throughout life. In addition, R-catenin was degraded in PGC bY GSK3β (glycogen synthase kinase-3β) -mediated ubiquitination, thereby nuclear accumulation of β-catenin being inhibited. 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 terabomas, but instead showed germ cell deficiency. The germ cell defiaciency resulted from aberrant cell cycle progression. Thus, inhibition of Wnt/β-catenin signaling is essential for PGC proliferation
(2) Role of PI3K/Akt signal in mouse PGC development and ES cell pluripotency
PTEN is a lipid phosphatase that antagonizes action of PI3K. PGC-specific PTEN knockout mice developed testicular teratomas and showed increased rates of RG cell formation. These results revealed that PI3K signaling is an important regulator which determines the development to germ lineage and dedifferentiation to pluripotent stem cells. We have established Akt-expressing mouse ES cell lines. The ES cells showed LIF (leukemia inhibitory factor) -independent maintenance of pluripotency. Furthermore, Akt-expressing primate ES cells retained pluripotency without the support of feeder cells. These results indicate that PI3K/Akt signaling regulates "stemness" in wide variety of stem cell systems.
|
