| 研究実績の概要 |
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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