Discovery of novel molecular mechanism to promote human cardiomyocytes survival

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K23950
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: KITANI Tomoya 京都府立医科大学, 医学部附属病院, 専攻医 (30842257)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: 心筋細胞 / 多能性幹細胞 / ゲノム編集

Outline of Final Research Achievements

We established human induced pluripotent stem cells (iPSCs) with a doxycycline-inducible Cas9 expression cassette at the AAVS1 safe harbor site. However, we found that there was a wide distribution of Cas9 expression in the cells even originated from a single cell clone. Next, we performed kinome-wide CRIPSR screen to find genes promoting cell survival under doxorubicin treatment in human cardiomyocytes derived from iPSCs. We found candidate genes to improve cardiomyocyte survival under doxorubicin treatment.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究ではヒト心筋細胞を用いることで、これまでの動物実験などでは不明であった心筋細胞の生存に重要な役割を持つ可能性のある遺伝子を明らかにすることができた。今後本研究の成果を発展することで、新たな心臓病の治療法の開発につながる可能性があると期待している。