Since the discovery of SNPs in immune genes as AD-risk factors, microglia have been further highlighted in human neurological health and disease. Several of these AD-GWAS genes, including CD33 and CR1, lack functionally-similar murine orthologs. Thus, iMGLs can be utilized to investigate AD-GWAS genes and elucidate their roles in human microglia biology. Aβ fibrils upregulated APOE, TREM2, CD33, and APOJ, genes previously implicated in modulating Aβ phagocytosis and clearance (Bradshaw et al., 2013; Yeh et al., 2016). We also found that MS4A6A gene expression was increased. While the role of the MS4A gene cluster in microglia function and AD risk is still unknown, our data suggests a potential role in modulating Aβ interactions. Furthermore, CD200 and CX3CL1 were important developmental CNS cues for generating iMGLs that can respond appropriately to Aβ. These data implicate these factors in modulating promoter/enhancer regions that enables appropriate responses to stimuli previously shown for macrophages (Gosselin et al., 2014; Lavin et al., 2014)(further reviewed in (Glass and Natoli, 2016). Lastly, a TGFβ-dependent homeostatic microglia signature was identified that paralleled murine studies and highlight that AD
