Elucidation of the Mechanism of Functional Decline of Aged Hematopoietic Stem Cells and Attempts to Restore Their Function.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17370
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Koide Shuhei 東京大学, 医科学研究所, 特任研究員 (10845126)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 造血幹細胞 / 老化 / 造血器腫瘍 / シングルセル解析

Outline of Final Research Achievements

In this study, HSCs were collected from young, middle-aged, and aged mice, and single cell RNA-sequence analysis was performed to elucidate the molecular mechanisms of age-related functional decline in the transcriptome. The analysis revealed that the dysfunctional HSCs observed in aged mice were already manifested in middle-aged mice, and that the molecular chaperone Clusterin (Clu) was highly expressed in these mice.
Analysis of Clu reporter mice revealed that Clu-positive cells dominantly increase with age and that age-related hematopoietic defects are attributable to Clu expression.

Free Research Field

造血幹細胞

Academic Significance and Societal Importance of the Research Achievements

近年世界的な高齢化を背景として、老化研究に対する高い注目が集まっている。本研究内容である造血幹細胞の老化は、加齢関連疾患としてしられる造血器腫瘍発症の母地として機能すると考えられている。
本研究成果として、加齢造血幹細胞の機能不全マーカーであるCluの同定に成功した。今後、Cluの発現制御を試みることで、白血病を始めとした老化関連疾患の予防、並びに治療法確立が期待される。