Endothelial cell heterogeneity and mechanism of diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03435
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kanazawa University (2021-2023); Osaka University (2020)
• Principal Investigator: Naito Hisamichi 金沢大学, 医学系, 教授 (30570676)
• Co-Investigator(Kenkyū-buntansha): 坂野 公彦 奈良県立医科大学, 医学部, 講師 (40865630)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 血管内皮細胞 / シングルセル解析 / 細胞多様性 / 血管内皮幹細胞 / 疾患特異的血管内皮細胞

Outline of Final Research Achievements

Vascular endothelial cells (VECs) exhibit functional and morphological heterogeneity. However, current vascular research assumes that all VECs are essentially the same and that cellular heterogeneity is due to environmental factors. We previously challenged this concept and demonstrated that there is cellular heterogeneity in VECs at the differentiation stage. In this study, we aim to develop our previous research and elucidate the cellular heterogeneity of VECs using single-cell RNA sequencing analysis, with the goal of establishing a new classification of these cells. By establishing the concept of cellular heterogeneity in VECs, we also aim to reevaluate the pathogenesis of various diseases. As a result, we show that VECs exhibit heterogeneity at the gene expression level, and we showed that targeting specific clusters of vascular endothelial cells could be feasible for treating diseases. Elucidating the microenvironment of VEC clusters will be essential for future study.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

血管はさまざまな疾患病態と深く関わる。日本人の死因の上位を占める悪性疾患、心疾患、脳血管障害も血管が深く関与する。本研究では血管の機能に重要な血管内皮細胞に着目した。血管内皮細胞は均一な細胞であるとされているが、本研究を通じて血管内皮細胞は非常に多様性を示すことが明らかになった。さらには疾患ごとにその多様性はさらに複雑になった。血管内皮細胞の細胞多様性を標的とすることで、疾患の制御ができる可能性を明らかにできた。将来的にはさまざまな疾患治療に応用できる新規治療法の開発につながる可能性がある。