2018 Fiscal Year Final Research Report

The fate of aneuploid cells

Research Project

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Project/Area Number	15H02398
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	一般
Research Field	Cell biology
Research Institution	Mie University
Principal Investigator	Inagaki Masaki 三重大学, 医学系研究科, 教授 (30183007)
Co-Investigator(Kenkyū-buntansha)	後藤英仁三重大学, 医学系研究科, 特任准教授(研究担当) (20393126) 笠原広介三重大学, 医学系研究科, 准教授 (90455535) 猪子誠人愛知県がんセンター(研究所), 腫瘍医化学部, 主任研究員 (30393127) 井澤一郎愛知県がんセンター(研究所), 腫瘍医化学部, 室長 (20311441) 田中宏樹愛知県がんセンター(研究所), 腫瘍医化学部, リサーチレジデント (20725452)
Project Period (FY)	2015-04-01 – 2019-03-31
Keywords	染色体異数性 / 中間径フィラメント / 細胞質分裂 / 老化 / がん化
Outline of Final Research Achievements	Intermediate filaments (IFs) are dramatically reorganized during mitosis. Some protein kinases activated in mitosis control spatial and temporal IF reorganization through IF phosphorylation. Here, we analyzed the dorsal skin wound healing in phospho-vimentin-deficient mice. In response to skin injury, vimentin expression was elevated at wound areas of subcutaneous fibroblast in a genotype-independent manner. During the acute phase of wound healing when vimentin expression was relatively high, IF-bridge formation, binuclation, and extra-centrosome formation was observed specifically in fibroblast of phospho-vimentin-deficient mice. These cellular structures disappeared with decreased expression, leading to increased numbers of aneuploid fibroblasts. Subsequently the fibroblasts exhibited a significant elevation of major senescence-relative markers. These abnormalities resulted in implicated wound healing, one of the premature aging phenotypes.
Free Research Field	分子生理学
Academic Significance and Societal Importance of the Research Achievements	aneuploidy（染色体異数性）はがん発生において直接的な引き金になるのかという生物学的に非常に重要な問いに対して、、本研究成果は、間葉系組織で高効率にanuploid細胞が生じる遺伝子改変マウスにおいては、むしろ白内障や皮下脂肪減少、創傷治癒遅延といった老化症状を引きおこうすことを示した。さらに、aneuploidyから老化に至る分子メカニズムの糸口となりうるモデルマウスの開発に成功した。