| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
The bone marrow microenvironment comprises multiple cell niches derived from bone marrow mesenchymal stem cells (BM-MSCs). However, the molecular mechanism of BM-MSC differentiation is poorly understood. The transcription factor GATA2 is indispensable for hematopoietic stem cells (HSCs) function as well as other hematopoietic lineages, suggesting that it may maintain BM-MSCs in immature state and also contribute to their differentiation. To explore this possibility, we established BM-MSCs from human bone marrow. GATA2 loss- and gain-of-function analyses based on human BM-MSCs confirmed that decreased and increased GATA2 expression accelerated and suppressed BM-MSCs differentiation to adipocytes, respectively. When GATA2 knockdowned BM-MSCs were cocultured with CD34+ cells, HSC frequency and colony formation decreased, indicating that decreased GATA2 expression induced BM-MSC differentiation, particularly into adipocytes, leading to the decreased hematopoietic supporting capacity.
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