Study for the mechanism of epithelial plasticity induced by the shift of mitotic spindle orientation

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H05004
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Developmental biology
• Research Institution: Tohoku University
• Principal Investigator: Nakajima Yuichiro 東北大学, 学際科学フロンティア研究所, 助教 (90782152)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 細胞分化 / 上皮間葉転換 / 細胞極性 / 細胞可塑性 / 細胞分裂方向 / 腫瘍

Outline of Final Research Achievements

Although EMT has been studied in vivo and in the developmental context, aberrant EMT, which mimics certain human pathogenesis, has not been systematically investigated due to the lack of tractable in vivo model.To characterize the initial cellular events following spindle misorientaiton, I took a live imaging approach to monitor the localization of junction and polarity proteins and examine the cytoskeletal dynamics during misoriented cell division and the following basal movement. In order to characterize the molecular signatures of EMT effects, I performed genome-wide transcriptional profiling by isolating mesenchymal-like cells via FACS and performing RNA sequencing analyses in both epithelial and mesenchymal-like cells. By defining the cellular and molecular features of spindle misorientation-induced EMT, this project has established a general mechanistic understanding of EMT events in proliferating epithelia.

Free Research Field

発生遺伝学、細胞生物学、発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で注目した分裂期スピンドル方向の異常で誘導されるEMTにおいては、上皮性の喪失と間葉への運命転換を遺伝子発現レベルで確認することができた。また間葉様細胞で発現がみられたEMT転写因子の発現によっても分裂方向の異常が誘導されたことから、分裂期スピンドル方向の異常を起点としたフィードバックの仕組みがEMT形質の獲得に寄与する可能性が示唆された。EMTは腫瘍の悪性化の様々な段階に関与することを考慮すると、上皮の分裂期スピンドル方向の異常が誘導する腫瘍の発生を体系的に明らかにすることは、ヒトにおける腫瘍発症機序の理解の向上につながると考えられる。