Fig. 6: Cellular ontogeny shapes chromatin accessibility in CNS macrophages.

a, Experimental scheme. Mrc1^CreERT2R26^tdT mice were injected with TAM and either treated with BLZ945 or CTL. CPs were removed and MG, CD206⁺tdT⁺ and CD206⁺tdT⁻ sdCAMs, CD206⁺tdT⁺ and CD206⁺tdT⁻ dCAMs as well as Ly6C^hi blood monocytes were sorted for scATAC-seq. Cells pooled from n = 3 (CTL) and n = 4 (BLZ945) mice. b, UMAP based on called peaks of 10,224 individual nuclei with cell type annotation. c, Bar graph depicting all significant differentially accessible peaks between BLZ945 and CTL for each cell type. d, Volcano plots comparing accessible peaks in MG and sdCAMs from 8w after BLZ945 to CTL. Bonferroni-corrected P values. NS, P > 0.05. e, Feature plots depicting module scores derived from selected differential gene activities between hom_ys_sdCAM and hsc_sdCAM. f, Coverage plots of Colec12 and H2-Aa loci depicting the aggregated ATAC reads for each cell subtype. Differentially accessible peaks are highlighted in gray. g, Venn diagram showing overlap of differentially accessible peaks in the BLZ945 compared to CTL condition for the depicted cell types. h,i, Feature plot displaying a repopulation module score calculated from differential gene activities that are commonly and significantly enriched in macrophages from BLZ945-treated animals compared to CTL (i). Coverage plot of the Zfp932 locus depicting the aggregated ATAC reads for each cell cluster. Differentially accessible peak is highlighted in gray.