2018 Fiscal Year Final Research Report
The determiniation of megakaryocyte lineage commitment of hematopoietic stem cells(Fostering Joint International Research)
| Project/Area Number |
15KK0350
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Research Collaborator |
Suda Toshio National University of Singapore, Cancer Science Institute, Principal investigator
MacArthur Ben D.
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| Project Period (FY) |
2016 – 2018
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| Keywords | 造血幹細胞 / 巨核球 / 単一細胞シークエンス解析 / 分化 / ミトコンドリア代謝 |
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| Outline of Final Research Achievements |
Hematopoietic stem cells (HSCs) are heterogeneous in differentiation potential. We analyzed BM HSCs for the identification of novel HSC subsets that are biased to Mk differentiation and the mechanism of how these HSCs emerge. We identified the cytokine, Thpo, rapidly skews HSC to Mk lineage differentiation. International collaboration with researchers in National University of Singapore enabled us to conduct single cell RNA sequence of HSCs from mice treated with Thpo. The data revealed that Thpo-treated HSCs were highly enriched with mitochondrial-related gene signature. The correlation of high mitochondrial content to Mk lineage differentiation was also confirmed in steady state HSCs with high mitochondria content. We also conducted ATAC sequencing in order to investigate change in chromatin accessibility in HSCs upon Thpo signaling. Collectively, our data indicate that mitochondrial metabolism and epigenetic changes maybe key mechanisms underlying Mk-lineage differentiation.
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| Free Research Field |
実験血液学
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| Academic Significance and Societal Importance of the Research Achievements |
急激な出血や重度の炎症の際、生体は止血のために早急に血小板を産生する必要がある。このため、造血細胞のおおもととなる造血幹細胞は血小板を産生する巨核球細胞に偏って分化傾向を示す細胞群があることが示唆されている。当研究は、造血幹細胞の巨核球系への分化運命の決定のメカニズムを解析した。シンガポール国立大学の研究室と共同研究と行い、造血幹細胞の巨核球系の分化にサイトカインのひとつであるトロンボポエチンのシグナルが関与していることを解析した。また、同時にミトコンドリア代謝、エピジェネティック変化の解析を行った。
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