2022 Fiscal Year Final Research Report
Elucidating the functional regulation mechanism of the hematopoietic microenvironment (niche) by the shelterin factor
Project/Area Number |
20H03711
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Kyushu University |
Principal Investigator |
Arai Fumio 九州大学, 医学研究院, 教授 (90365403)
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Co-Investigator(Kenkyū-buntansha) |
細川 健太郎 九州大学, 医学研究院, 講師 (90569584)
八尾 尚幸 九州大学, 医学研究院, 助教 (90835282)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | POT1 / 間葉系幹細胞 / 造血幹細胞 / ニッチ |
Outline of Final Research Achievements |
This study investigated the function and aging regulation of mesenchymal stem cells (MSCs), the primary niche cells of hematopoietic stem cells (HSCs). We focused on the functional role of the shelterin factor POT1a in regulating MSC. MSC function, which declines with aging, is postulated to be involved in the functional decline of HSCs. This study found that POT1a maintains the stem cell activity of MSCs and their capacity to differentiate into osteoblasts and suppresses their functional decline with aging. In addition, the study showed that loss of POT1a reduced the hematopoietic supportive capacity of MSCs and impaired HSC function. These findings suggest that POT1a is essential in maintaining MSCs and their function as niche cells. The results of this study may be a crucial step toward establishing methods for the prevention and treatment of aging-related hematologic diseases.
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Free Research Field |
幹細胞生物学
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Academic Significance and Societal Importance of the Research Achievements |
MSCの老化は、骨芽細胞への分化能力の低下を伴い、これが骨粗鬆症などの疾患発症につながる可能性がある。本研究では、老化がMSC内のPOT1aの発現を低下させる一方で、POT1a導入により老化したMSCの骨分化能力が回復することを明らかにした。これらの結果から、POT1が加齢に伴う骨関連疾患の治療ターゲットとなる可能性を示している。さらに、MSCの機能異常はHSCの機能低下、リンパ球の産生減少、そしてそれに続く免疫機能の低下につながる可能性がある。したがって、老化したMSCでPOT1の機能を活性化できれば、それは高齢者の造血機能や免疫機能の回復を可能にする基盤となると考えられる。
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