Mechanism Underlying Hematopoietic Stem Cell Aging via the Disruption of Multilayered Chromatin Structure

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Chiba University
• Principal Investigator: Nakanishi Mio 千葉大学, 大学院医学研究院, 講師 (70534353)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 老化 / 造血幹細胞 / 分化バイアス / 休止 / エピジェネティクス / アポトーシス

Outline of Final Research Achievements

This study aimed to elucidate the unknown intrinsic mechanisms of aging in hematopoietic stem cells (HSCs) that cause systemic inflammatory aging and to identify its inducers. To achieve this, the research employed a highly sensitive epigenetic modification analysis method to examine HSCs from young and old mice. It found that key characteristics of HSC aging, such as differentiation bias towards certain cell lineages (myeloid bias), maintenance of quiescence, and the survival of mutated cells, are all underpinned by epigenetic changes. Additionally, the study demonstrated the association between the loss of expression of several blood differentiation-related transcription factors and aging in HSCs.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では造血幹細胞老化の主要な特徴である分化の偏り（ミエロイドバイアス）や休止維持・変異細胞の生存がエピジェネティック変化を基盤とすることを示した。さらにこのようなエピジェネティック変化と分化制御転写因子との関連を示唆した。これらは将来的な抗老化医療の重要なターゲットをもたらすものである。今後本研究の成果を基盤として、さらに多細胞間の造血レジリエンス制御変容を理解することにより、未知の老化メカニズム解明が進むことが強く期待される。