CX3CL1 and CD200 are both neuronal- and endothelial-derived cues that can further educate iMGLs toward an endogenous microglia phenotype (reviewed in (Kierdorf and Prinz, 2013). To test this hypothesis, we examined how inclusion or exclusion of these factors modulates iMGL phenotype. The addition of CD200 and CX3CL1 to iMGLs increased the expression of select genes like COMT (Bennett et al., 2016)(Figure S5B), CD52, a cell surface receptor that binds Siglec-10 and interacts with DAP12 as part of the microglia sensome (Hickman et al., 2013) and HLADRB5, a member of the MHC II complex implicated in AD, while maintaining similar expression levels of core-microglial genes (e.g. P2RY12, TYROBP, OLFML3) and AD-risk genes (Figure S6A). Importantly, we found that CD200 and CX3CL1 modulated iMGL response to CNS stimuli, such as fAβ. In the absence of CD200 and CX3CL1, fAβ stimulated the expression of AD-GWAS genes implicated in interacting with misfolded folded protein, surface receptors, or anti-apoptotic events such as CLU (APOJ) (Yeh et al., 2016). Whereas cells exposed to these two factors responded differentially to fAβ, increasing expression of genes involved in
