The Study of Molecular Mechanism to Establish Cardiac Progenitor's Identity

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03647
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yashiro Kenta 京都府立医科大学, 医学(系)研究科(研究院), 教授 (60432506)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 心臓前駆細胞 / 分化運命決定 / シングルセル解析 / マルチオミクス解析 / シグナル経路 / 細胞間相互作用 / エンハンサー

Outline of Final Research Achievements

In our previous work, we have originally found that gene X, whose name is not disclosed here due to intellectual property reasons, and Gfra2 gene can identify “an intermediate state” between cardiac mesoderm and cardiac progenitor cells (CPCs). Based on this original knowledge, we aimed to better understand the molecular mechanism underlying the establishment of CPCs’ identity, which remains still largely unknown. We elucidated comprehensively the signals, cell-cell interactions and differentiation pathways from cardiac mesoderm to CPCs via an intermediate state, with single cell study and enhancer analysis for gene X. Then, we found: (1) CPCs’ identity is robustly induced, likely by some specific signals, (2) chromatin remodeling is unlikely primary for this process, and (3) approximately 300 bp of genomic region of gene X locus is sufficient and essential for the expression among cardiac cells. Based on this novel knowledge, we will further explore what induces CPCs’ identity.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

我々の研究から得られたデータにより、心臓中胚葉から分化しCPCsとしての自己を確立する分子機構の一端が明らかとなった。得られた新たな知見をもとに、次の課題である「CPCsへとロバストな分化を誘導するスイッチは何か」を解析する起点を得られたと考えている。CPCsの機能的異常は先天性心疾患の原因になり得るため、今後はそのような疾患の背景にある分子病態の理解をさらに深め、新たな治療開発へ基盤的知見を提供する研究を期待できる。また、そのような知見は、多能性幹細胞から心臓再生医療に用いる心筋細胞を得る効率を上げ、労力とコストの削減と質の向上に大きく貢献することも期待される。