| Budget Amount *help |
¥191,490,000 (Direct Cost: ¥147,300,000、Indirect Cost: ¥44,190,000)
Fiscal Year 2018: ¥37,050,000 (Direct Cost: ¥28,500,000、Indirect Cost: ¥8,550,000)
Fiscal Year 2017: ¥36,920,000 (Direct Cost: ¥28,400,000、Indirect Cost: ¥8,520,000)
Fiscal Year 2016: ¥37,050,000 (Direct Cost: ¥28,500,000、Indirect Cost: ¥8,550,000)
Fiscal Year 2015: ¥36,920,000 (Direct Cost: ¥28,400,000、Indirect Cost: ¥8,520,000)
Fiscal Year 2014: ¥43,550,000 (Direct Cost: ¥33,500,000、Indirect Cost: ¥10,050,000)
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| Outline of Final Research Achievements |
We analyzed mouse hematopoietic stem cells (HSCs) and found that polycomb repressive complex 2 (PRC2) target genes marked with H3K27me3 moderately reduce H3K27me3 levels at their promoters in aged HSCs, resulting in the activation of PRC2 target gene signature in aged HSCs. Several aging stresses such as infection and myeloablative stresses attenuated the function of PRC2 like aging. In addition, PRC2 insufficiency in mice accelerated the development of age-related myeloid malignancies, such as myelodysplastic syndrome, in concert with driver mutations. These data suggest that a decline in PRC2 activity is associated with HSC aging and age-related clonal HSC disorders. Age-related decline in PRC2 activity could be one of the epigenomic determinants that facilitate expansion of HSC clones with founding driver.
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