Fig. 2.
Bulk and single-cell sequencing reveals JADE1 mRNA is modulated by rs56405341 and upregulated in tangle-bearing neurons. a Bulk RNA sequencing data yielded a significant lead SNP (rs56405341) eQTL (p = 0.038) in the dorsolateral prefrontal cortex of 452 postmortem human brain samples. Expression of JADE1 decreases with in subjects carrying the minor allele. Single cell sequencing data of populations of neurons with and without neurofibrillary tangles isolated from human post-mortem brain samples separated using fluorescence-activated cell sorting and transcriptomic profiles from single-cell RNA-sequencing were subsequently analyzed. b In 2 unique excitatory neuronal populations (Ex1 and Ex2) JADE1 mRNA was significantly differentially expressed in the tangle bearing neurons (adjusted p = 7.82 × 10−8, 4.55 × 10−15); in comparing the overall population of tangle-bearing excitatory neurons (Ex-total) to non-tangle bearing neurons the difference is highly significant (adjusted p = 1.04 × 10−61). c, d Other two genes in the locus, C4orf33 and SCLT1, were overall nominally expressed in both excitatory neuronal groups, as well as subclusters (Supplementary Fig. 5 b, c, online resource). e Dot plot showing average relative expression and percent expression of the candidate genes in the locus. Both JADE1 relative average expression and percentage of cells expressed was higher than C4orf33 and SCLT1. f, g t-Distributed stochastic neighbor embedding (tSNE) plots showing the different populations neurons, tangle bearing status, and relative expression of JADE1 in neuronal subpopulations