Deciphering regulatory mechanism of trained immunity in aged HSCs and clonal hematopoiesis of indeterminate potential (CHIP)

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In the original research proposal, the objective was to investigate the functional impact of induced trained immunity in aged hematopoietic stem cells (HSCs) and its role in the pathogenesis of clonal hematopoiesis of indeterminate potential (CHIP).During FY2022, the focus was on establishing a humanized mouse model by transplanting human cord blood-derived HSCs. The initial step involved establishing a connection with a cord blood bank to acquire fresh samples of human cord blood. A protocol was then developed to obtain high-quality CD34+ HSCs through cell sorting. Additionally, several immunodeficient mouse models were carefully selected to assess their compatibility for human HSC transplantation and evaluate the survival rates of humanized mice. The survival of humanized mice with aging depends on selective mouse strains and HSCs engraftment. Following the transplantation of HSCs (CD34+) into the humanized mice, the differentiation of these cells into mature immune cells has been clearly characterized and delineated.To achieve the research goals, investigations are underway to identify genetic mutations in the target genes of the sorted human cord blood HSCs (CD34+ cells).