Extended Data Fig. 5: Epigenetic divergence of transcriptome-based supertypes across mouse cortical areas.

(a) UMAP of multiome ATAC data colored by aPir, pPir, AI, and SSp datasets. Neurons are integrated using Harmony. (b) UMAP as in (a) colored by the corresponding transcriptome-based supertype. For interneurons areas mix, while for glutamatergic neurons piriform separates from SSp, while AI overlaps with both (see (a)). (c) UMAP as in (a) colored by epigenome-based leiden clusters. (d) Mapping of transcriptome-based clusters (RNA, supertypes) to epigenome-based (ATAC, leiden) clusters. For glutamatergic neurons, multiple area-specific epigenome-based clusters correspond to a single supertype. Adjusted Rand Indices (ARIs) quantify the cluster overlap: for all neurons= 0.43; for INs= 0.88; for glutamatergic neurons= 0.37. (e) High-quality e-regulons are selected for downstream analysis based on the correlation between AUC (Area Under the Curve) scores for target genes and target CREs (Cis Regulatory Elements). A correlation cut-off of 0.4 and a minimum number of target genes of 10 are used. (f) Upset plot of the intersection of target genes for the e-regulon Rorb(+), which is shared across aPir, pPir, AI and SSp. Vertical bars show the number of target genes in the corresponding intersection of the matrix below. Horizontal bars show the total number of target genes for each cortical area. Of note, main text states 9% overlap between aPir and SSp target genes. That overlap is computed with a Jaccard similarity index and equivalent to taking in the upset plot the (relative) size of a combination of intersections. (g) Upset plot of the intersection of target CREs for the e-regulon Rorb(+). See (f) for details. (h) From left to right, average log-normalized expression of target genes (TGs) of Rorb identified in aPir, pPir, AI, and SSp. TGs of a given area are shown across areas (even if they are regulated by other TFs). (i) Difference of gene expression between target genes identified in aPir and SSp for the e-regulon Rorb(+) remains within a 2-fold change. The average log- normalization expression (y-axis) is only used to spread data points. (j) From left to right, average log-normalized expression of a random set of genes (n = 500) for aPir, pPir, AI, and SSp, similar to (h). Expression patterns are qualitatively equivalent as in (h). (k) Difference of gene expression between set of random genes in aPir and SSp datasets remains within a 2-fold change and indicates that Rorb TGs in (i) behave as a set of random genes.