Fig. 4: MITF is a key DAM regulator and driver of phagocytosis.

a, Volcano plot of differentially accessible peaks according to ATAC-seq of iMGLs exposed to ANs compared with untreated. Peaks with false discovery rate (FDR) ≤ 0.05 are shown in magenta. b, Intersection of transcription factors nominated by ATAC-seq and SCENIC analysis. c, UMAP projection of iMGL dataset (as in Fig. 1a) showing MITF expression in iMGLs treated with CNS substrates. d, Volcano plot of differentially expressed genes (DEG) in the iMGLs overexpressing MITF (n = 4) compared with those overexpressing mCherry (n = 4). Blue indicates top downregulated genes, dark red indicates top upregulated genes and orange indicates genes involved in DAM signature and lipid metabolism. Blue line represents adjusted FDR ≤ 0.05. P adj, adjusted P value. e, Quantification of MITF expression in iMGLs transduced with mCherry-expressing and MITF-expressing lentivirus (two-tailed t-test, P = 0.0129, mean and s.d. are shown; n = 4 for each condition). f, Bar graph of gene ontology analysis for MITF-overexpression DEG. Bar length represents the number of genes, and shading represents statistical significance. g, Venn diagram of overlap between DEG in iMGL samples transduced with MITF-expressing versus mCherry-expressing lentivirus, and DEG in iMGL_02 and iMGL_8; hypergeometric test, P = 1.098 × 10⁻¹². h, Comparison of MITF-overexpression genes with iMGL states; numbers of genes and P values from the hypergeometric test are shown. i, Quantification of GPNMB expression (left, two-tailed t-test, P = 0.0159, *P < 0.05) and LPL expression (right, two-tailed t-test, P = 0.0042, **P < 0.01) in RNA sequencing samples as in d. j, Mean intensity of pHrodo-conjugated AN in iMGLs transduced with either MITF or mCherry (two-tailed t-test, P = 0.0051, **P < 0.01; n > 5 for each condition). In all bar graphs, error bars represent s.d.