2017 Fiscal Year Final Research Report
The role of CD109 and TGF-beta for the preferential commitment of PIGA mutant HSPCs in immune-mediated bone marrow failure.
| Project/Area Number |
15K09496
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
NAKAO Shinji 金沢大学, 医学系, 教授 (70217660)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 再生不良性貧血 / CD109 / TGF‐β / PIGA遺伝子変異造血幹前駆細胞 |
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| Outline of Final Research Achievements |
To determine whether a TGF-beta (b) co-receptor CD109 on hematopoietic stem progenitor cells (HSPCs) play a role in the preferential commitment of PIGA mutant HSPCs in patients with immune-mediated bone marrow failure (BMF), we established CD109-knock out (KO) TF-1, a GM-CSF-dependent myeloid leukemia cell line, using the CRIPR/Cas9 system, and compared the sensitivity of CD109KO TF-1 cells to TGF-b to that of wild-type (WT) TF-1 cells. The TGF-b treatment induced pSMAD2 in CD109KO TF-1 cells to a significantly lesser degree than in WT TF-1 cells. The proliferation of CD109KO TF-1 was inhibited by TGF-b also to a lesser degree than WT TF-1 cells. The results suggest that CD109, a glycosylphosphatidylinositol anchor protein, plays an enhancing role in the TGF-b signaling in HSPCs, and the lack of CD109 may make the HSPCs less sensitive to TGF-b, leading to the preferential commitment of the PIGA mutant HSPCs in immune-mediated BMF, in which TGF-b suppresses activation of WT HSPCs.
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| Free Research Field |
血液内科学
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