Fig. 6: Two distinct types of cPcdh diversity distinguish fetal and adult brain tissues.

a, Heatmap, H3K4me3 ChIP-seq signal on α/γ-cPcdh promoters relative to the highest enrichment observed in each sample (as a percentage over max, or 100%). Sample scheme on top, samples listed in Supplementary Fig. 19a. Postmortem human brains: fetal, n=2 donors, gestational stage=17-pcw, or post-conception weeks; fetal, germinal matrix, n=2 donors, 20-pcw; and, adult brain, n=3 donors, range=73–81 year-old, n=7 independent samples. Neurospheres from postmortem fetal brain, n=4 donors, range=15–17-pcw. The most H3K4me3-enriched γ-promoters in human fetal brains are indicated (black dots). Dendrogram, hierarchical clustering analysis of the same samples shown in the heatmaps; one minus Spearman-rank correlation. Samples color-coded by source. b, Heatmap, RNA-seq signal (RPKM, exonic, BrainSpan cohort) of α/γ-cPcdh genes in the n=524 postmortem samples of the human developing and adult brain (ranging from 4-pcw to 40+ years of age and a variety of different brain regions⁴²). Data not available for four γ-isoforms (in blank). Profiles, RNA-seq signal (RPKM, BrainSpan) for non-stochastically selected cPcdhs and neuronal and glial markers. The most H3K4me3-enriched γ-promoters in fetal brains are highlighted (black dots). c, Mean differential methylation with 95% confidence intervals (CI) on stochastically selected (blue circles) and non-stochastically selected (grey circles) α/γ-promoters (top/bottom panels) in postmortem brain samples of control and Down syndrome subjects, as indicated in the upper/lower side of each panel (sample numbers and additional labeling provided in Supplementary Fig. 21; Supplemental Note). Background colored based on interquartile range (IQR, pink) and upper/lower quartiles (blue/green) of stochastically selected promoters.