Fig. 4

Identification of 326 phagocytic AD MG DEGs and relevant function. A Functional-validated human Aβ phagocytic AD MG DEGs. The embedded dashed box shows identification of 184 upregulated and 193 downregulated Aβ + MG DEGs in GSE165306. MG were isolated from the Cerebrum of AD 5xFAD tg mice injected with florescent Methoxy-X04 (MeX04) that labels Aβ plaque and sorted for Aβ + and Aβ − populations for further scRNA-seq analysis. The Aβ + MG DEGs were identified with FC ≥ 1.5 and adjusted p-value < 0.05 and overlapped with the previously identified functional-validated human AD MG DEGs. B The functional-validated mouse Aβ phagocytic AD MG DEGs were identified by overlapping the Aβ + MG DEG with the previously identified mouse AD MG DEGs using the same strategy in A. C Identification of phagocytic modifier AD MG DEGs. MG genetic modifiers of phagocytosis were identified by conducting a phagocytic genetic modifier screening using CRISPR-Cas9 for knockout of genes encoding membrane proteins, drug targets, kinases, or phosphatases in the BV2 cell line derived from phagocytic microglia (PMID: 30,944,478). The Venn diagram shows the overlap of BV2 cell phagocytic modifier genes with AD MG DEGs of human and mouse. D Gene sets related to endocytosis. A total of 2172 genes involved in biological processes of endocytosis, exocytosis, and transcytosis were collected from GO, KEGG, Reactome, and WikiPathways. E Overlapped endocytosis-related AD MG DEGs. The overlap analysis of 2172 endocytosis-related genes with 409 human and 777 mouse AD MG DEGs identified 16 overlapped endocytosis-related AD MG DEGs in human and mouse. F Total phagocytic AD MG DEG is summarized. Aβ, amyloid beta; AD, Alzheimer’s disease; DEG, differentially expressed gene; FC, fold change; i, inhibit; i.p., intraperitoneally; MeX04, Methoxy-X04; MG, microglia; MIF, macrophage migration inhibitory factor; p, promote; SC, single cell; TGN, trans-Golgi-network