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Chunk #32 — DISCUSSION

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Transcriptional and anatomical diversity of medium spiny neurons in the primate striatum.
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the sequencing depth was most similar between the studies. Co-clustering our data with the mouse data revealed that approximately half of the D1H population co-clustered with D1/D2-hybrids, and the other half co-clustered with D1-NUDAPs (Figures S3A-S3C). However, despite their similarities and their co-clustering with D1H, our data indicate that D1-NUDAP neurons and D1/D2-hybrid neurons represent distinct MSN subtypes. First, although DRD2 expression was common in D1/D2-hybrids (Figures 2D and 4F), we found no evidence of DRD2 expression in D1-NUDAPs (Figures S7A and S7B). Second, the D1-NUDAP neurons did not express other marker genes, including CASZ1 and GRIK1, that were reported in D1/D2-hybrids, D1H, and eSPNs.15-17 Third, a machine learning classifier easily distinguished between D1-NUDAP and D1/D2-hybrid neuron subtypes (Figure 2E). Finally, we only found D1/D2-hybrid MSNs in the DS, whereas D1-NUDAP cells were restricted to dense cell islands in the VS. Together, these data clearly demonstrate that in NHPs, D1-NUDAP and D1/D2-hybrid MSNs are discrete subtypes. However, the limitations involved with integrating single cell data sets,54,55 and the vast differences between the studies – differences that include species, age, single cell technology, transgenic status, MSN sampling density, and sequencing depth – preclude us from determining the role of species in