Figure 3. Single nucleus RNA-seq in human brains reveals that the AD protective variant rs1582763 alters a specific microglia population and drives the expression of genes associated with chemokine and lipid metabolism pathways.
A. Schematic of single nucleus brain RNA-seq. B. UMAP reveals a significant increase in the proportion of a specific population of microglia (Mic.3) in the presence of the rs1582763 minor allele (A) (The fraction below indicates the proportion of Mic.3 in the total microglia of given genotype carriers). C. MS4A4A expression is significantly elevated in Mic.3 in the presence of the minor allele of rs1582763 (Kruskal-Wallis test, p = 1.11 x 10−2). D. Bar graph of the number of genes differentially expressed as a function of the rs1582763 genotype across microglia subclusters reveals that differentially expressed genes are enriched in Mic.3. Grey, p<0.05. Black, FDR<0.05. E. Volcano plot of genes differentially expressed based on rs1582763 genotype in Mic.3. F. Pathway analysis reveals that rs1582763 alters genes within Mic.3 that influence immune response, lipid metabolism, protein degradation and calcium regulation.