2009 Fiscal Year Final Research Report
Search for genes involved in the maintenance of glioma stem cells
| Project/Area Number |
20790245
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Yamagata University |
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Principal Investigator |
SUNAYAMA Jun Yamagata University, 医学部, 助教 (80466606)
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| Project Period (FY) |
2008 – 2009
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| Keywords | glioma / stemness |
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| Research Abstract |
Control of stem cell state and differentiation of neural stem/progenitor cells is essential for proper development of the nervous system. EGF and FGF2 play important roles in the control of neural stem/progenitor cells, but the underlying mechanism still remains unclear. Here we show, using in vitro primary cultures of mouse neural stem/progenitor cells, that both PI3K and mTOR are activated by EGF/FGF2 but that inhibiting the activation of either PI3K or mTOR alone results in only reduced proliferation of neural stem/progenitor cells without affecting their stem cell state, namely, the capacity to self-renew. However, significantly, concurrent inhibition of PI3K and mTOR promoted exit from the stem cell state together with astrocytic differentiation of neural stem/progenitor cells. These findings suggest that PI3K and mTOR are involved in the EGF/FGF2-mediated maintenance of neural stem/progenitor cells and that they may act in parallel and independent pathways, complementing and backing up each other to maintain the stem cell state. These findings are also expected to help understand the molecular mechanism by which glioma stem/initiating cells are maintained, given the similarity between neural stem cells and glioma stem cells.
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