signature targets including P2RY12, TGFβR1, and CD33, and transcription factors EGR1 and ETV5, and APOE (Figure S5A–C). Examination of gene ontology highlight neurodegenerative disease pathways including AD, Parkinson’s, and Huntington’s diseases that are TGFβ dependent (Figure S5D). Furthermore, removal of TGFβ led to significant changes in many of the human microglia homeostatic targets also identified as AD GWAS loci genes including TREM2, APOE, ABCA7, SPI1 (CELF1 locus), PILRA (ZCWPW1 locus), and the HLA-DR and MS4A gene clusters (Karch et al., 2016), suggesting many identified AD GWAS genes function in the maintenance of microglia homeostasis (Figure S5E) and underscoring the utility of iMGLs to interrogate AD GWAS gene function.
