| 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)
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| 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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