Fig. 6: Non-cell-autonomous effects of SST+ interneurons on cortical progenitors. | Nature Communications

Fig. 6: Non-cell-autonomous effects of SST+ interneurons on cortical progenitors.

From: DNMT1-mediated regulation of somatostatin-positive interneuron migration impacts cortical architecture and function

Fig. 6

a, b Ligand-receptor interactions between SST+ cINs to (a) RGC and (b) IPCs, extracted from differentially expressed genes (DEG; scRNA sequencing of E14.5 dorsal telencephalons (N = 5)). Dot color: communication probability; dot size: one-sided permutation test p-values. c–g Pair cell assay using E14.5 cortical neurons treated for 24 h with control-Fc or ephrinB2-Fc, followed by immunostaining for nestin (NES, magenta), β-III-tubulin (TUBB3, green), EOMES (yellow), and DAPI (blue). c Experimental design. Representative images are shown in (d, f). Scale bars: 5 µm. e, g Quantification of NES/NES (2xN), TUBB3/TUBB3 (2xT), NES/TUBB3 (N-T), EOMES-EOMES (2xE), and NES-EOMES (N-E) cell pairs, normalized to the total pair count. Unpaired two-tailed Welch’s t-test with control-Fc: n = 90 cell pairs, efnB2-Fc: n = 91 cell pairs, from N = 4 experiments in (e); and control-Fc: n = 90 cell pairs, efnB2-Fc: n = 94 cell pairs, from N = 4 experiments in (g). h–m snRNA sequencing of cortical cells from E16.5 Sst-Cre/tdTomato (Ctrl) and Sst-Cre/tdTomato/Dnmt1 loxP2 (KO) embryos (n = 2 brains from N = 2 mice per genotype). h UMAP of identified cell clusters. i Dot plot of marker gene expression across clusters. j Bar plot: proportions of postmitotic excitatory neurons. k Venn diagram: overlap of upregulated genes in E14.5 FAC-sorted cortical KO cells (bulk RNA sequencing) and E16.5 cortical Sst+/Gad+ KO cells (snRNA-seq). l, m CellChat-derived interaction maps (E16.5 cortical snRNA-seq data): number (l) and strength (m) of inferred cell–cell interactions in KO vs. Ctrl. n–q MERFISH-based spatial transcriptomics (E16.5; n = 1 section for KO and Ctrl, respectively). n UMAP of identified cell clusters by gene expression. o Spatial mapping of clusters onto anatomical regions in E16.5 sections, scale bar: 1000 µm. p Magnified sections from the cortex depicted in (o). Scale bar = 100 µm. q Cluster annotation for (n–p). *p < 0.05, **p < 0.01, ***p < 0.001, error bars: ±SEM. n.s.: not significant. Raw data are available via the hyperlinks listed in the data availability statement, Supplementary Data 10.

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