Fig. 4: Characterization of specialized regulatory landscape of GABAergic neurons.

a The UMAP visualization (left) and relative percentage (right) of GABAergic LAMP5 and LAMP5/LHX6 cell subclasses among humans, macaques and mice. b Dot plot showing the transcription factor binding site (TFBS) activities in LAMP5/LHX6 GABAergic neurons across species. c Relative ratio of LAMP5/LHX6 vs. LAMP5 cell subclasses in various macaque cortical regions. d UMAP embedding of LAMP5/LHX6 neurons (left) and normalized gene activity score of PROX1 and NOS1 (right). e Volcano plot showing the differentially enriched DORCs in PROX1⁺ and NOS1⁺ populations of LAMP5/LHX6 neurons. Differential enrichment was defined as adjusted P-value < 1×10⁻⁵ and |log₂FC | > 0.75. f The number of distal CREs linked to TSS region of PROX1. g Genome browser track view showing two primate-specific distal CREs linked to TSS region of NOS1 in LAMP5/LHX6 cell clusters. h UMAP embedding of GABAergic SST neurons labeled with their layer specificity. i Gene regulatory networks for layer-specific SST neuron groups. j Genome browser track showing two differential accessible distal CREs linked to KIRREL3 in L2/3 SST neurons. The two CREs harbor binding motifs of TF KLF7. k Spatial visualization of chromatin accessibility of two CREs linked to KIRREL3 in SST neurons in representative sections at different coordinates in EBZ numbers (left). The bar plot illustrates the mean chromatin accessibility of CREs across different layers (right). The sample sizes are listed in Supplementary Data 10. Error bars represent SEM. l Boxplot showing chromatin accessibility of two CREs linked to KIRREL3 (upper/lower correspond to left/right in k) in SST neurons across cortical lobes. P values were calculated by Kruskal-Wallis test. The sample sizes are listed in Supplementary Data 10. Center line, median; box limits, 25th–75th percentiles; whiskers, 1.5 × IQR; points beyond, outliers.