The molecular mechanism of ectopic differentiation from the study of DNA-damage response of Melanocyte Stem Cell.
Project/Area Number |
22790377
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Single-year Grants |
Research Field |
Experimental pathology
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
AOTO Takahiro 東京医科歯科大学, 難治疾患研究所, 助教 (90457599)
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Project Period (FY) |
2010 – 2011
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Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 幹細胞 / 皮膚 / 細胞分化 / DNA損傷応答 / 白髪 / DNA修復 |
Research Abstract |
I have previously shown that genotoxic stress, including X-ray or free-radical species, abrogate self-renewal of melanocyte stem cell and leads to the depletion of the functional melanocyte, and this is one of the mechanism for the hair graying during the aging process. Although malignant melanoma is known to be caused by the mutation of various oncogene or tumor suppressors in melanocyte lineage, the precise origin of proliferative melanoma cells in the tumors has been unknown. In this study, melanomagenic-genotoxic stress, including UV or DMBA, induce the increased number of melanocyte stem cell, and can antagonize hair graying inductive genotoxic stress. I found that the difference between hair graying-and melanomagenicinductive stress is caused by the response of the niche, rather than the melanocyte stem cells per se, after the differential genotoxic stress. I found that niche derived secreting factor after the melanomagenic stress can support the self-renewal of melanocyte stem cells and bypass the hair graying in vitro and in vivo. Collectively, these data indicate the choice between tissue aging and tumorigenesis is determined by the complex interplay of stress response between the stem cell and niche.
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Report
(3 results)
Research Products
(15 results)