Fig. 3

Transcriptomic analysis of astrocytic nuclei in control and HD. a Three-dimensional t-distributed stochastic neighbor embedding (tSNE) plot showing astrocytic nuclei (n = 1064–469 control and 595 HD) colored as red (Control) or blue (HD), reduced into three dimensions. b Three dimensional tSNE plot showing the classification of the astrocytic nuclei into 6 sub-clusters using consensus k-means clustering (sc3 package). c Gene expression heat map of cluster markers showing nuclei (Columns) and specific cell-type markers (Rows). Condition (Con versus HD) and Cell-types are color-coded on the top and bottom, respectively. Cluster-specific gene markers were identified using Wilcoxon signed rank test comparing gene ranks in the cluster with the highest mean expression against all others. p-values were adjusted using the “Holm” method. The genes with the area under the ROC curve (AUROC) > 0.65 and p-value< 0.01 are shown as marker genes. d-e GO term analysis of differentially expressed genes in HD versus control astrocytes identified using EdgeR likelihood ratio test with an adjusted p.value of 0.05. Significantly enriched GO terms at Benjamini-Hochberg false discovery rate of 0.05 were identified. Selected Reactome pathways and Molecular function GO terms which are increased in HD astrocytes (d) and decreased in HD astrocytes (e) are shown