Elucidation of organ protection effect by new understanding of blood cell social structure

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19475
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: FUJIU KATSUHITO 東京大学, 医学部附属病院, 特任教授 (30422306)
• Co-Investigator(Kenkyū-buntansha): 小島 敏弥 東京大学, 医学部附属病院, 病院診療医(出向) (30625588) ; 荷見 映理子 東京大学, 医学部附属病院, 特任助教 (70599547) ; 中山 幸輝 東京大学, 医学部附属病院, 助教 (70721885) ; 杉田 純一 東京大学, 医学部附属病院, 病院診療医(出向) (70755694)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: バーコード / 造血幹細胞 / マクロファージ / 心臓

Outline of Final Research Achievements

This study utilized DNA barcoding to investigate how heart failure (HF) affects the differentiation capabilities of hematopoietic stem cells (HSCs). The findings revealed that HSCs exposed to HF have an increased ability to generate circulating monocytes but a reduced ability to generate tissue macrophages in the heart and kidneys. This indicates that HF induces long-term epigenetic changes in HSCs, leading to altered differentiation pathways that contribute to systemic inflammation and tissue damage. The barcode analysis demonstrated the diversity among HSC clones, highlighting that different clones specialize in generating specific cell types, such as monocytes or tissue macrophages. These findings provide insights into how HF-induced stress affects HSC function and how this contributes to the progression of heart failure and related comorbidities.

Free Research Field

内科学

Academic Significance and Societal Importance of the Research Achievements

この研究は、心不全が造血幹細胞の分化能力に与える影響を解明し、心不全や併存疾患の進行メカニズムを明らかにしました。これにより、心不全の新たな治療法開発に向けた基盤が提供され、医療現場での患者ケア向上につながる可能性があります。