Fig. 6

Differential chromatin accessibility associated with the GABAergic neuron lineages in different brain regions. A. Circosplot showing the hierarchical clustering dendrogram of dominantly (> 75%) GABAergic clusters (n = 52) in E14.5 mouse brain, barplots of the proportion of cells by the brain region of origin, and the heatmap of the average expression of proneural gene Ascl1, GABAergic fate selector genes Dlx1, Dlx2, Gata2, Gata3, Tal2 and Tal1 and the GABAergic neuron marker genes Gad1 and Gad2. The clustering by chromatin accessibility loosely correlates with the brain region and the selector gene expression. D/DL R1, dorsal/dorsolateral R1; VL, ventrolateral. Asterisk indicates the cell clusters where MAPT and Tubb3 are found among the top 25 of differentially expressed genes. B. Chromatin accessibility based pseudotime trajectory and placement of the Dlx1 and Dlx2 expressing GABAergic cell clusters and progenitor cell clusters 80, 150 and 48. Cluster subdivision performed internally by VIA are shown on the left side, with colored pie charts indicating composition of each subcluster, where the numbers indicate original cluster number having majority in the corresponding subcluster. Lines with arrows indicate lineage relations and direction between nodes. The image on the right side shows the same lineage structure, with each subcluster colored according to estimated pseudotime. The red-framed circles indicate the lineage end points. The size of the circles is proportional to the number of cells in the cluster. The lineages representing the diencephalic prosomere 3 (P3), medial ganglionic eminence/ preoptic area (MGE/POA) and lateral and caudal ganglionic eminence of telencephalon (LGE/CGE) GABAergic neurons are indicated, along with the relevant marker gene expression. C. Heatmap of the inferred RNA expression in Dlx1/2 expressing GABAergic neuron clusters. Hierarchical clustering is based on the expression of top 1400 most variable genes. Both axes have been clustered with Euclidean distance and ward.D2 linkage. scATAC-seq cluster of origin and the lineage placement of cluster is shown on the right for each cell. D. Heatmap of the total length of the DA chromatin in Dlx1/2 expressing sublineages. The cell clusters were clustered by the similarity in the differentially accessible (DA) DNA features. E. Heatmap of the chromatin accessibility for features within ± 50 kpb around Gad2 gene (columns) across GABAergic clusters (rows). Dominant brain region of origin is shown in the parenthesis after cluster number. Barplots on the right side show average expression of Gad2 in the cluster