Gene expression profile of microglia and border-associated macrophages carrying hDNMT3A mutation
To probe for the impact of a age-related clonal hematopoiesis associated somatic mutation on monocyte-derived microglia and macrophages in the CNS, we took advantage of a mouse model that harbors a replacement of the murin Dnmt3a gene with a cDNA cassette encoding the human DNMT3A R882H variant. To seed the CNS with monocyte-derived cells from hDNMT3A mut hematopoietic stem cells, we engrafted Cx3cr1-gfp mice with bone marrow of 10-month-old Vav-Cre: hDNMT3A fl/fl mice. After 4 months following irradiation, endogenous microglia and leptomeningeal macrophages, and engrafted cells were isolated from both mutation and wild type groups for bulk RNAseq analysis. Overall design: Cx3cr1 gfp/+ mice were lethaly irradiated, and took either Vav-Cre: hDNMT3A fl/fl or hDNMT3A fl/fl bone marrow. After 4 months of irradiation, both GFP+ and GFP- microglia and leptomeningeal macrophages were isolated from both Mut and WT groups for sorting.