| Budget Amount *help |
¥117,650,000 (Direct Cost: ¥90,500,000、Indirect Cost: ¥27,150,000)
Fiscal Year 2018: ¥22,750,000 (Direct Cost: ¥17,500,000、Indirect Cost: ¥5,250,000)
Fiscal Year 2017: ¥22,750,000 (Direct Cost: ¥17,500,000、Indirect Cost: ¥5,250,000)
Fiscal Year 2016: ¥22,750,000 (Direct Cost: ¥17,500,000、Indirect Cost: ¥5,250,000)
Fiscal Year 2015: ¥22,620,000 (Direct Cost: ¥17,400,000、Indirect Cost: ¥5,220,000)
Fiscal Year 2014: ¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000)
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| Outline of Final Research Achievements |
We have previously reported that p53 is activated in blood vessels by various stresses and contributes to tissue dysfunction and metabolic abnormalities. We hypothesized that hematopoietic insults also affect bone marrow vascular niche. We herein demonstrated that p53 becomes activated in BM endothelial cells upon hematopoietic stresses such as irradiation and chemotherapeutic treatments. The conditional activation of p53 in VE-cadherin+ vascular niche cells by deleting Mdm2 induced the expression of p53 target genes specifically in vascular endothelial cells, resulting in the dilation and collapse of vascular endothelial cells and reductions in perivascular mesenchymal stromal cell numbers. Consequently, hematopoietic stem cells (HSCs) failed to maintain dormancy, mobilized to the periphery, and were significantly depleted. Our results indicate that various hematopoietic insults affect HSCs not only directly, but also indirectly by altering vascular integrity.
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