Prevention of age-related deregulation of hematopoietic stem cell function through the protection of telomeric DNA

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293228
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyushu University
• Principal Investigator: Arai Fumio 九州大学, 医学(系)研究科(研究院), 教授 (90365403)
• Research Collaborator: MacArthur Ben D. サウサンプトン大学
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 造血幹細胞 / Pot1a / テロメア / 非対称分裂

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.

Free Research Field

幹細胞生物学