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Chunk #7 — Results — High quality single nuclei transcriptomics identifies canonical and low abundant cell types in human dorsal striatum

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Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder.
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We used multiple rounds of graph-based clustering, and cell label transfers from a high-quality, high-resolution snRNA-seq non-human primate striatum dataset to cluster and annotate striatal cell types34,35 (Fig. 1d, Supplementary Data 1-S1). The first round of clustering identified major cell classes of glia and neurons (primary marker): astrocytes (AQP4 + ), endothelial cells (CLDN + ), microglia (CX3CR1 + ), mural cells (CD44 + ), oligodendrocytes (ASPA + ), oligodendrocyte precursors (OPC; PDGFRA + ), and neurons (RBFOX3 + , GAD2 + ) (Fig. 1d, e). The second round identified major striatal neuronal subtypes, including medium spiny neurons (MSN; PPP1R1B + ) and interneurons (LHX6 + ) (Fig. 1d, e). Among MSNs, we identified various canonical subtypes, consistent with our non-human primate dataset36, including DRD1+ and DRD2+ neurons accompanied by markers that distinguish neurochemical compartments, the striosome (KCNIP1 + ) 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 + ,