Elucidation of molecular features of cardiac endothelium specific angiocrine factors

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08397
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Chiba University
• Principal Investigator: YOKOYAMA Masataka 千葉大学, 大学院医学研究院, 助教 (20514871)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: アンギオクライン因子 / 心疾患 / 心臓血管内皮細胞 / 心筋細胞

Outline of Final Research Achievements

We performed single-cell analysis on endothelial cells isolated from mouse hearts and confirmed the co-expression of four selected transcription factors at the application stage. It was revealed that these factors are not uniformly expressed in all endothelial cells but rather form heterogeneous combinations. Furthermore, each transcription factor was found to have different direct regulatory mechanisms, with one particularly showing abundant binding near the promoter region, suggesting its potential role as a core promoter. By creating cell lines overexpressing these transcription factors in combination, we established a transplantation model for injured myocardium. As a result, we identified that two factors are essential for engraftment, and the accompanying third factor revealed the molecular expression patterns.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

血管内皮細胞が臓器特異的な役割を担っていることが最近の研究から示唆されていたが、その特異性に関わる転写因子群が同定されたことに意義がある。今後病的な血管あるいは機能破綻につながる要素として司る分子解明を繋げ、生活習慣を含めた予防的な介入が視野に入る。例えば心臓病における寄与の大きい動脈硬化病変において、このような特異的分子の状態を解明する方向に、今後の展開を広げていくことができる。