Graduate School of Medicine, Chiba University千葉大学大学院医学研究院― 47 ―With aging, tissue stem cells often show various functional declines such as depletion or disordered proliferation, as well as a bias in differentiation towards specific lineages. In the case of hematopoietic stem cells, aging results in a decrease in quiescent cells and a significant increase in the number of stem cells defined by cell surface markers. Concurrently, there is a decline in transplantability, clonalization, loss of differentiation ability towards the lymphoid lineage, and abnormal differentiation bias towards the myeloid lineage (myeloid bias), presenting various functional declines. Such aging of hematopoietic stem cells is thought to promote chronic inflammation throughout the body through the increased production of inflammatory immune cells, driving the progression of various age-related diseases and being a major process in the inflammatory aging of the individual.Despite the various functional declines, variations in gene expression in aging hematopoietic stem cells are relatively minor, and reports suggest that the functional recovery of aging hematopoietic stem cells transplanted into young bone marrow is limited. These findings imply that epigenetic changes, rather than changes in the stem cell microenvironment or gene expression variations, might be the primary cause of functional decline in aging hematopoietic stem cells. However, due to technical difficulties such as the necessary cell numbers, epigenetic analysis of rare hematopoietic stem cells, particularly the analysis of histone modification states, had not progressed. Therefore, this study attempted to elucidate the mechanisms of hematopoietic stem cell aging using a sensitive, comprehensive, and high-precision histone modification analysis method.As a result of comprehensively analyzing histone modifications in aging hematopoietic stem cells using Abstract組織幹細胞老化メカニズムの解明とその抑止法の探索Elucidation…of…the…mechanism…of…tissue…stem…cell…aging…クロマチン３次元構造破綻によるdue…to…chromatin…3D…structure…disruption…andthe…exploration…of…its…inhibition…methods中西 未央Mio Nakanishi
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