show Abstracthide AbstractThe role of the lineage-determining transcription factor IRF8 in microglia remains unelucidated. We report the genome-wide, transcriptome profiles of wild-type, IRF8KO, IRF8cKO, Batf3KO, 5xFAD, and 5xFAD/IRF8KO microglia. Deep-sequencing and subsequent differential analysis revealed the impacts of IRF8 on microglia-specific transcription programs, such as cell identity. Sall1 and Batf3 genes were identified as a downstream transcription factor of IRF8, and Batf3 dependent genes showed correlation with IRF8-dependent genes in microglia. The conditional depletion of IRF8 gene after microglial maturation (P14) increased or decreased the gene expression, most of which were shared with those of IRF8KO. This study provides a novel insight into understanding transcriptional programs in microglia. Overall design: Transcriptome profiles of adult WT, IRF8KO, 5xFAD, 5xFAD/IRF8KO, IRF8cKO, and Batf3KO mice were analyzed. The conditional deletion of IRF8 gene was achieved with 5 consecutive days of Tamoxifen injection to an IRF8flox-Cx3cr1CreERT2-Rosa26LSL-EYFP mouse at the age of P12-14 and YFP-positive microglia at 3-month-old of age were sorted and analyzed.