Fig. 1: A subset of ASD risk genes are expressed by microglia and their perturbation shifts the activation state of iPSC-derived microglia (iTF-Microglia).

A Stacked bar graph comparing the relative expression of 102 ASD risk genes [16] in neurons and microglia. B UMAP derived from single cell transcriptomic data for iTF-Microglia with CRISPRi-mediated knockdowns targeting 53 ASD risk genes involved in gene regulation. Each dot represents a single cell colored by gene target. C UMAP displaying the expression of the microglia marker, IBA1, encoded by AIF1 for individual cells. D (Left) UMAP displaying the results of transcriptomic cluster analysis for which each color represents a unique cluster. (Right) Dot plot showing the expression of each cluster’s top three differentially expressed genes. The color of the dots reflect the relative expression of the gene in a given cluster, and the size of the dots represent the percent of cells expressing the gene in a given cluster. E, F UMAPs displaying the distribution of cells containing sgRNAs targeting 12 specific ASD risk genes or non-targeting controls (NTCs). Blue dots represent the target cell and gray dots represent all other cells. G Stacked bar graph comparing the cluster occupancy by cells containing sgRNAs targeting 12 specific ASD risk genes or NTCs. Bar segments are colored according to cluster identity. H Individual bar graphs for the three activation clusters showing the change in cluster occupancy relative to NTCs. I Scatterplot showing the change in the interferon and chemokine clusters relative to NTCs.