Developmental cellular origins and regulatory mechanisms of differentiation in calcified lesions

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20917
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0903:Organ-based internal medicine and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Iwase Akiyasu 東京大学, 大学院医学系研究科(医学部), 特任助教 (10965130)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 石灰化 / 細胞起源 / 神経堤細胞

Outline of Final Research Achievements

Spatiotemporal histological analysis of the calcified lesion formation was performed in a mouse model of calcification pathology using warfarin. The results revealed that calcified lesions occur in the aorta and coronary arteries and are associated with calcification of various origins in Wnt1-Cre; R26-EYFP mice labelled with neural crest cells and Islet1-Cre; R26-EYFP mice labelled with cells derived from secondary heart field. In silico analysis, the CARTA algorithm was developed to identify enhancer-like candidates between arbitrary transcription factors and target genes from single-cell ATAC-seq data, identifying common enhancer-like regions in embryonic heart and human coronary artery calcification lesions.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

我が国の死因第2位を占める心血管疾患において、石灰化はその病態の進展や有害事象の発症に深く関与し、治療法の選択にも影響を与える重要な病態である。臨床的に抗凝固剤として用いられるワーファリン投与は副作用として石灰化が報告されており、治療法を探索する上でも本研究は重要な位置づけとなる。特に細胞起源や領域性、そして発生過程で見られるエンハンサーとの共通性などの制御機構を含めた知見は新規治療法開発の基盤となるものである。