Analysis of signal transduction pathways which maintain pluripotency of primate embryonic stem cells.
Project/Area Number |
15609003
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
幹細胞生物学
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Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
SUEMORI Hirofumi KYOTO UNIVERSITY, Institute For Frontier Medical Sciences, Associate Professor, 再生医科学研究所, 助教授 (90261198)
|
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: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
Keywords | Embryonic stem cell / LIF / STAT3 / Pluripotency / primate / 霊長類 / ヒトES細胞 / 未分化性 |
Research Abstract |
The leukemia inhibitory factor/glycoprotein 130/signal transducer and activator of transcription 3(LIF/gp130/STAT3) pathway plays an essential role in the maintenance of self-renewal and pluripotency in mouse embryonic stem(ES) cells. In primate ES cells, including those from humans and monkeys, however, LIF alone is not sufficient to maintain self-renewal. The precise role of the LIF/gp130/STAT3 pathway for self-renewal in primate ES cells is still unclear. Here, we found that stimulation of cynomolgus monkey ES cells with LIF or IL-6/sIL-6R leads to STAT3 phosphorylation, an effect seen previously in murine ES cells. Concomitant with this notion, nuclear translocalization and transcriptional activation of STAT3 were observed in a LIF-dependent manner. Moreover, the analysis of a dominant interfering mutant, STAT3F, showed that even though the phosphorylation, nuclear translocalization, and transcriptional activation of endogenous STAT3 following LIF stimulation were completely abrogated by overexpressing STAT3F in monkey ES cells, they continued to proliferate in an undifferentiated state, retaining their pluripotency. These results demonstrate that the LIF/gp130/STAT3 pathway functions in cynomolgus monkey ES cells but is not essential for the maintenance of self-renewal. They also suggest that cynomolgus monkey ES cells, unlike murine ES cells, are maintained in an undifferentiated state through LIF/gp130/STAT3-independent signaling.
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Report
(3 results)
Research Products
(2 results)