Establishing a rapid and highly efficient method for in vivo direct reprogramming of fibroblasts into epithelial lineages using mesenchymal-to-epithelial transition program(Fostering Joint International Research)

2022 Fiscal Year Final Research Report

• Project/Area Number: 16KK0165
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Watanabe Kazuhide 国立研究開発法人理化学研究所, 生命医科学研究センター, 客員主管研究員 (40749397)
• Project Period (FY): 2017 – 2022
• Keywords: 生体内リプログラミング / 間葉上皮移行 / 転写因子 / OVOL2 / 表皮細胞 / エピゲノム

Outline of Final Research Achievements

We have developed a method of reprogramming fibroblasts into epidermal cells by combining transcription factors. In this study, we proposed to explore in vivo direct reprogramming potential by applying this technology. However, due to the spread of COVID19, it has become difficult to carry out our research at the overseas destination. Therefore, we took an alternative approach by using cultured cells and by analyzing existing data. As a result, we discovered that the activation of BMP signals can induce the expression of OVOL2 and promote chemical reprogramming from fibroblasts to epidermal cells. These results are important findings that contribute to the development of new in vivo reprogramming technologies.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では当初の目的であった生体内ダイレクトリプログラミング法の確率は果たせなかったが、高効率で線維芽細胞を表皮細胞に転換する新しいケミカルリプログラミングの開発を進めることができた。これの成果により、最終ゴールである生体内ダイレクトリプログラミング法の確立を加速することができると考えられる。この生体内リプログラミング法が確立できれば、例えば広範囲熱傷の患者さんの自身の組織を用いた表皮再形成の促進を促すなど、臨床応用への期待が持てる。v