CSF1R-G795A microglia engraft and respond to neuroinflammation in the adult murine brain. (A) Schematic depicting neonatal HPC injection paradigm, with endpoints (black ticks) at 60 d and after LPS injections, and LPS injection paradigm (blue line). (B) Volcano plot comparing differential gene expression by RNA-seq between G795A- and WT-xMG 2 mo after transplantation (FDR ≤ 0.05; log₂(FC) ≥ ±1). (C and D) Linear regression analysis and the coefficient of determination between WT- and G795A-xMG when examining the full transcriptome (C; R² = 0.74–0.95) and a 249-gene microglia signature (D; R² = 0.78–0.97). (E) Immunostaining for IBA1+ (green)/Ku80+ (red) WT- and G795A-xMG demonstrates decreased expression of P2RY12 (purple) in response to LPS treatment. (F and G) Conversely, WT- and G795A-xMG increase expression of CD45 (F; white) and MX1 (G; blue) in response to LPS treatment. Representative 40× images. Scale bar, 50 µm. (H–K) Quantification of E–G. One-way ANOVA IBA1 (P = 0.5061); P2RY12 (P < 0.0001); CD45 (P = 0.0007); MX1 (P = 0.0003). Tukey’s HSD; **P < 0.01, ***P < 0.001, ****P < 0.0001. Data represented as mean intensity normalized to number of Ku80+/IBA1+ human microglia per FOV for all antibodies calculated from three matched coronal sections per animal (n = 3 biological replicates). Error bars, SEM.