2019 Fiscal Year Annual Research Report
Role of inflammation in initiation and progression of clonal hematopoiesis
| Project/Area Number |
18F18408
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| Research Institution | Kumamoto University |
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| Host Researcher |
滝澤 仁 熊本大学, 国際先端医学研究機構, 特別招聘教授 (10630866)
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| Foreign Research Fellow |
FAKRUDDIN MD. 熊本大学, 国際先端医学研究機構, 外国人特別研究員
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| Project Period (FY) |
2018-10-12 – 2021-03-31
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| Keywords | クローナル造血 / 炎症 |
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| Outline of Annual Research Achievements |
The hematopoietic stem cells (HSCs) in the bone marrow provide all types of blood cells throughout life by their self-renewal and multi-lineage differentiation abilities. Inflammation, infection and aging induce mutations which triggers abnormalities in HSCs and such abnormal HSCs are predisposed to myeloproliferative diseases. Lineage tracing of such predisposed HSCs will provide valuable insight on clonal hematopoiesis and factors that contribute to CHIP (Clonal Hematopoiesis of Indeterminant Potential). This study was aimed to develop novel method for clonal tracing that can be used both in vitro and in vivo and by applying this method, to elucidate role of inflammation in the development of CHIP.
Accomplishment update
Mice with Poly-IR tag and HSB with be exposed to inflammatory stress and/or infection and mononuclear cell fraction will be sorted from the peripheral blood of those mouse after HSB induction, using the mouse of Objective 1-B), and target 1-A) and the number and size of clones will be determined by the method developed in this study. The hematopoietic stem cell / progenitor cell fraction of the bone marrow will be re-evaluated after a certain period of time. Comparing clonal dynamics between different treatments will help us to identify HSC clones with proliferative advantage and CHIP potential.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
現在までのところ、DNAバーコードを検出技術の立ち上げとそれを持つモデルマウスのESクローンを樹立したところで今後はマウスを作製する必要があるため
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| Strategy for Future Research Activity |
Cre発現依存的にスリーピングビューティーがオンになるマウスで目的コンストラクトを持つESを樹立して、マウス作成を一度試みたが、キメラマウスが生まれなかっため、今後も引き続きトライする。作成され次第、DNAバーコードマウスと交配して目的のマウスを作成する。その後、細菌感染などの炎症を起こし、造血幹細胞クローンの進展、拡大への影響を評価する。
Expected outcome
Upon successful evaluation of the method developed in this study in mouse model, it will provide useful tools not only in the field of hematopoietic stem cells but also in other biomedical research fields such as stem cell and cancer biology to trace lineage to single cell resolution. The knowledge obtained from this study is expected to provide contribution towards establishment of preventive methods for pre-leukemia initiation and progression.
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