Prevention of age-related deregulation of hematopoietic stem cell function through the protection of telomeric DNA
Project/Area Number |
26293228
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Kyushu University |
Principal Investigator |
Arai Fumio 九州大学, 医学(系)研究科(研究院), 教授 (90365403)
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Research Collaborator |
MacArthur Ben D. サウサンプトン大学
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
|
Keywords | 造血幹細胞 / Pot1a / テロメア / 非対称分裂 / DNAダメージ / 活性酸素種 / 内科 / 再生医学 / 細胞分裂制御 / DNA損傷応答 / 自己複製 / 細胞分裂 / テロメアDNAダメージ |
Outline of Final Research Achievements |
Hematopoietic stem cells (HSCs) maintain life-long hematopoiesis by their unique ability to both self-renew and differentiate along multiple lineages. The decision of stem cells to undergo self-renewal or differentiation occurs through asymmetric and symmetric cell divisions. However, age-related accumulation of intracellular stress such as DNA damages can negatively affect their divisions and thereby inhibit HSC function. Here, we found that Pot1a, a component of telomere-specific protein complex Shelterin, improved HSC activity during aging by protecting telomeres against DNA damage and preventing metabolic alterations and the production of reactive oxygen species. Transduction of Pot1a maintained the ability of HSCs to undergo the self-renewal division in culture. These data suggest that Pot1a supports HSC function via telomeric and novel non-telomeric roles and indicate that Pot1a is essential for the protection of HSC function and maintenance of healthy aging.
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Setdb1 maintains hematopoietic stem and progenitor cells by restricting the ectopic activation of non-hematopoietic genes.2016
Author(s)
Koide S, Oshima M, Takubo K, Yamazaki S, Nitta E, Saraya A, Aoyama K, Kato Y, Miyagi S, Nakajima-Takagi Y, Chiba T, Matsui H, Arai F, Suzuki Y, Kimura H, Nakauchi H, Suda T, Shinkai Y,Iwama A.
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Journal Title
Blood
Volume: 128(5)
Issue: 5
Pages: 638-649
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Self renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance.2016
Author(s)
Ito K, Turcotte R, Cui J, Zimmerman SE, Pinho S, Mizoguchi T, Arai F, Runnels JM, Alt C, Teruya-Feldstein J, Mar JC, Singh R, inkel T, Suda T, Lin CP, Frenette PS, Ito K
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Journal Title
Science
Volume: 354(6316)
Issue: 6316
Pages: 1156-1160
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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