| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
Congenital amegakaryocytic thrombocytopenia (CAMT) is caused by the loss of thrombopoietin receptor (MPL)-mediated signaling, which causes severe pancytopenia leading to bone marrow failure with onset of thrombocytopenia and anemia prior to leukopenia. We used an in vitro disease tracing system with iPSCs derived from a CAMT patient (CAMT-iPSCs) and normal iPSCs to investigate the role of MPL signaling in hematopoiesis. In this study, we found that1) MPL signaling is essential for maintenance of the CD34+multipotent hematopoietic progenitor (MPP) population and 2) for development of the CD41+Glycophorin-A (GPA)+ megakaryocyte-erythrocyte progenitor (MEP) population 3) complementation of appropriate expression level of MPL into CAMT-iPSCs using a retroviral vector improved potential of MK and erythrocyte differentiation 4) excessive MPL expression led to aberrant megakaryopoiesis and generation of GPIba and GPIV null platelets.These results recapitulate the clinical course seen in CAMT-patients in vitro and suggest importance of appropriate gene complementation as cell therapy for CAMT-patients.
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