Archetype analysis also highlighted continuous sources of variation within subtypes. Some nuclei derived from the VS clustered together with matrix nuclei (D1M and D2M). We detected archetypes that highlighted the VS nuclei fraction (Figure S3H), and the genes that were correlated with the VS weighted vector are preferentially expressed in NAc core, including ZDBF2 (r = 0.18 and 0.2, p < 10−6 and 10−7, with D1- and D2-MSNs, respectively, Pearson’s correlation) and HPCAL4 (r = 0.12, p < 10−3 with D2-MSNs, Pearson’s correlation) (Data S3).31 Another archetype of particular interest was found in D1Sh and defined by upregulation of the gene for the Neurokinin-B receptor, TAC3. Differential gene analysis of the D1Sh TAC3-archetype revealed selectively genes enriched in this archetype, including MPPED1, HPCAL1, and MEIS3. This result demonstrates within-subtype variations with potentially functional roles.
