CAMT-iPS Cells Exhibiting Defective MPL Signaling Dysregulate hematopoiesis
| Project/Area Number |
23791154
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Kyoto University |
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Principal Investigator |
TAKAYAMA Naoya 京都大学, iPS 細胞研究所, 助教 (10584229)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| 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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| Keywords | 疾患特異的iPS細胞 / CAMT / c-MPL / 巨核球分化 / 赤血球分化 / 造血不全 |
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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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Report
(3 results)
Research Products
(25 results)
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[Journal Article] CAMT-iPS Cells Exhibiting Defective MPL Signaling Dysregulate Megakaryopoiesis and Erythropoiesis.2013
Author(s)
Hirata S., Takayama N.(Corresponding author),Jono-Ohnishi R., Endo H., Nakamura S., Dohda T., Nishi M., Hamazaki Y., IshiiE.,Kaneko S., Otsu M., NakauchiH.,Kunishima S., and Eto K.
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Journal Title
Journal of Clinical Investigation
Related Report
Peer Reviewed
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[Journal Article] Role of SOX17 in hematopoietic development from human embryonic stem cells.2013
Author(s)
Nakajima-Takagi Y, Osawa M, Oshima M, Takagi H, Miyagi S, Endoh M, Endo TA, Takayama N, Eto K, Toyoda T, Koseki H, Nakauchi H, Iwama A.
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Journal Title
Blood.
Volume: 121
Issue: 3
Pages: 447-58
DOI
Related Report
Peer Reviewed
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[Journal Article] Heterozygous ITGA2B R995W mutation inducing constitutive activation of the {alpha}IIb{beta}3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia.2011
Author(s)
Kunishima S, Kashiwagi H, Otsu M, Takayama N, Eto K, Onodera M, Miyajima Y, Takamatsu Y, Suzumiya J, Matsubara K, Tomiyama Y, Saito H.
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Journal Title
Blood
Volume: 117
Pages: 5479-5484
Related Report
Peer Reviewed
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[Presentation] TRANSIENT ACTIVATION OF C-MYC EXPRESSION IS CRITICAL FOR EFFICIENT PLATELET GENERATION FROM HUMAN INDUCED PLURIPOTENT STEM CELLS2011
Author(s)
Takayama N, Nishimura S, Nakamura S, Shimizu T, Ohnishi R, Endo H, Yamaguchi T, Otsu M, Nishimura K, Nakanishi M, Sawaguchi A, Nagai R, Takahashi K, Yamanaka S, Nakauchi H, Eto K.
Organizer
XXIII Congress of the International Society on Thrombosis and Haemostasis
Place of Presentation
Kyoto, Japan
Related Report
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