Fig. 1

Bulk_RNASEQ. Transcriptomic analysis of Huntington disease cingulate cortex. Total RNA sequencing was done on 6 grade III/IV and 6 control cingulate cortices. a Sample distance (Manhattan method) heatmap clustered using the Ward method. b Mean-Expression plot showing log2 fold-change (LFC -HD versus control) on the y-axis, and mean normalized counts on the x-axis. Significantly differentially expressed genes are shown in red and blue for upregulated and downregulated genes, respectively. c Differential gene expression heatmap of select astrocytic genes as described in Liddelow et al. [27], with controls (Con) denoted by the red bar, and HD by the blue. Asterisks next to gene names indicate significance (Benjamini-Hochberg adjusted p value < 0.05 and absolute log fold change > = 1.5). A1, A2, and pan-reactive astrocytic genes are denoted. Asterisks below case numbers indicate which cases were selected for single cell nuclear RNAseq. d Representative GO ontology term analysis showing significantly increased Reactome pathways in HD cases from bulk RNAseq (using the gProfiler web-platform, Benjamini-Hochberg adjusted p-values set at < 0.05). e-f Gene set enrichment analysis of select astrocytic genes (Astrocyte markers and Astrocyte_differentiation -GO0048708). Normalized enrichment scores (NES) are shown