were specific to each of the neural cell types identified in human striatum. Collectively, we identified many transcription factors and gene regulatory modules per cell type (47 ± 15 specific modules; glial subtypes, 90 ± 19; neuronal subtypes, 12 ± 6; Fig. 1h; Supplementary Data 1-S4). For example, ZNF83 (HPF1) transcription factor-regulatory module was enriched in D1-matrix and D1-striosome MSNs, known to be involved in DNA damage repair. RXRG28,48,49 and FOXP250 transcription factor-regulatory modules were highly enriched in D1/D2-hybrid MSNs relative to other MSN subtypes, both of which are implicated in psychiatric disorders, including substance use51. ZNF202 was also highly enriched in D1/D2-hybrid MSNs–transcription factor involved in cellular metabolism and the direct modulation of dopamine receptor 3 (DRD3). Other modules included SOX952 and TCF7L253 enriched in astrocytes, and others in microglia, such as RUNX1, REL, and MEF2C, with the RB1 and NFIX54 modules enriched in oligodendrocytes (Fig. 1h). Together, the annotated cell type clusters in human dorsal striatum, their associated marker genes, and related transcription factor gene regulatory modules offer insights into the molecular signaling pathways that contribute to the heterogeneity of cellular identity in human striatum.
