Fig 1: Western, lipidomics, and cellular analyses validates HD differences in TPK1 and PRKCE.a Scatterplots of Z-score log2 fold change values comparing mouse and human data in 12w striatum versus human caudate OL DEGs. Genes with |Z-log2FC| values > 1 are highlighted in seafoam green and OL maturation genes are highlighted in orange, showing concordance between species for PRKCE and OL maturation genes, and discordance of TPK1 expression. b Western blot of PRKCE and phospho-PRKCE in HD and control patient cingulate cortex and caudate. c Quantification of western blot results. Two-tailed Mann Whitney test used for each statistical analysis. Exact p-values: Cingulate: PKCE-0.0003, p-PKCE-0.0003; Caudate: PKCE-0.0055, p-PKCE- 0.0385. n = 3 control and 11–12 HD caudate samples, and 5 control and 11–12 HD cingulate samples. Data shown as mean +/− SEM as error bars. d Licor images of Prkce, pPrkce, TPK1, and respective revert in R6/2 and NT striatum and cortex. e Quantification of licor results. One-way ANOVA used for statistical analysis. n = 6 NT and 6 R6/2, biologically independent samples. Data shown as mean +/− SEM as error bars. f Western blot of TPK1 in human caudate samples from juvenile HD, HD grades 1–4, and control patients. g Quantification of human TPK1. Statistical analysis was done using a one-way ANOVA and Tukey HSD posthoc, comparing control to each adult HD grades (adjusted p = 0.979, 0.221, 0.070, and 0.018) and control to juvenile HD (p = 0.015). Data shown as median (center line), first and third quartile (Inner quartile range, box), and min and max values as whiskers. h DAG levels quantified from HD and control patient brains showing significant decreased DAG levels in HD brains. One-way ANOVA and Tukey’s HSD posthoc used for statistical analysis, comparing control to each adult HD grades. n = 7 control, 3 HD1, 3 HD2, 2 HD3, 4 HD4, 8 HD-J, biologically independent samples. Data shown as median (center line), inner quartile range (box), and min and max values as whiskers. i Western blot of PRKCE, MOG, CNPase, OLIG2, and A-Tubulin in OPC and OLs +/− K/D of PRKCE. Two-tailed Mann Whitney test used for statistical analysis. n = 3 biologically independent samples per group. Data shown as mean +/− SEM as error bars. For western blot results, source data are provided as a Source Data file.