To investigate the molecular features of human dorsal striatum, we collected both caudate and putamen from unaffected individuals (n = 6, 3 females and 3 males, for each region). Unaffected individuals were then compared to individuals with OUD to identify cell type-specific molecular alterations associated with opioid addiction. Both striatal regions were dissected from frozen postmortem tissue samples and processed to generate nuclei suspensions for snRNA-seq (Fig. 1a, b). Quality control analyses yielded a total of 98,848 nuclei for subsequent analyses–~70% of overall nuclei captured were used for analysis with an average of 5757 and 3440 nuclei per caudate and putamen, respectively, yielding an average of 8237 nuclei per individual (Fig. 1c). Across individuals, the number of nuclei captured, and the percent of nuclei analyzed were consistent (p = 0.40, linear regression, Supplementary Data 1-S1). Each nucleus was deeply sequenced at a 70% saturation rate, detecting an average of 3513 ± 77 genes (mean ± standard error) and 13,635 ± 560 unique transcripts per nucleus per individual (Fig. 1c). The average number of genes detected and the number of unique
