and matrix (EPHA4 + ). We also identified less abundant neuronal subtypes including MSNs expressing both DRD1 and DRD2 (D1/D2-hybrid, known as eccentric MSNs, D1-Pcdh8+, or D1H in mice)17,34–37, mural cells, and several types of interneurons (e.g., CCK + , PVALB + , SST + , and TH + ; (Fig. 1d, e)38,39. D1/D2-hybrid MSNs expressed conserved marker genes largely distinct from D1- and D2-MSNs (Fig. 1e, Supplementary Data 1-S2). These D1/D2-hybrid MSNs co-express both DRD1 and DRD2 transcripts at the single cell level (Fig. S3), consistent with in situ mRNA hybridization and single cell RNA-seq data from both mice35,37,40 and non-human primates34. The average per cell type metrics showed more genes and unique transcripts in neurons (Number of genesNeurons = 7318 ± 125; UMsINeurons = 44,585 ± 1,301), compared to glial cells (Number of genesNeurons = 2911 ± 74; UMsINeurons = 8433 ± 349; Fig. S4). Further, proportions of low or high abundance striatal cell types were consistent across brain regions, between sexes, and between unaffected individuals and individuals with OUD (FDR = 0.25, mixed effects linear regression; Fig. 1f; Supplementary Data 1-S2). Overall, we captured a high-quality snRNA-seq dataset of postmortem human caudate and putamen that is deeply
