Fig. 8: Early KCC2-expressing INs are found in the human prenatal cortex and display exclusively upregulated synaptogenic and signaling genes and downregulated Sox4. | Nature Communications

Fig. 8: Early KCC2-expressing INs are found in the human prenatal cortex and display exclusively upregulated synaptogenic and signaling genes and downregulated Sox4.

From: Functional KCC2 expression marks an evolutionarily conserved population of early-maturing interneurons in the perinatal cortex

Fig. 8

a UMAP plots depict prenatal human interneuron (IN) clusters from single-nucleus RNA-seq data across gestational weeks (GW) 17–38, sample origin and KCC2 (SLC12A5) enrichment (INs in UMAPs: n = 16,625). b. Quantification reveals a progressive, significant increase in KCC2 expression across GW 17–38 (correlation = 0.1650, p = 3.80 × 10⁻⁹). Box plots show 25th percentile, median, and 75th percentile; whiskers extend to ≥ 1st quartile − 1.5× IQR and ≤3rd quartile +1.5 × IQR. The red line indicates linear regression. KCC2+ INs: n = 1259 (19.6% of 6426 INs). Per-GW IN counts: GW17 n = 7, GW18 n = 14, GW19 n = 5, GW20 n = 46, GW21 n = 204, GW22 n = 52, GW23 n = 37, GW24 n = 45, GW25 n = 113, GW26 n = 104, GW33 n = 464, GW38 n = 168. Human embryonic brains per GW: N = 1, except GW20, 26, 33 (N = 2). c Dot plots quantify enrichment of KCC2, SST, NPY, CALB1, GAD1, GAD2, DLX2, HTR3A, LHX6, NXPH1, NXPH2, PAX6, SP8, CXCL14 and MEIS2. d UMAP plots show SST, NPY, CALB1, GAD1, GAD2 and HTR3A enrichment in INs and the fraction of KCC2+ INs co-expressing each marker. e UMAP plot marks clusters selected for differential gene expression (DGE), Gene Ontology (GO), and SynGO analyses, with a Venn diagram of conserved DEGs. f Left: Volcano plot compares KCC2+ and KCC2− cells, highlighting significant DEGs (adjusted p < 0.05, |fold change| > 1.5), including upregulated synaptic genes and downregulated Sox4. Right: SynGO sunburst plot shows hierarchical enrichment of synaptic components; only colored tiles are significant. DEGs were identified with a two-sided Wilcoxon rank-sum test and Benjamini–Hochberg correction. g GO analysis shows DEGs enriched in biological processes and cellular components linked to connectivity and synaptic maturity in KCC2+ INs; Gene Ratio indicates the proportion of annotated DEGs. The top 15 terms are shown. Supplementary Data 4–8 provide detailed results.

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