Molecular programs of regional specification and neural stem cell fate progression in developing macaque telencephalon

Abstract

Early telencephalic development involves patterning of the distinct regions and fate specification of the neural stem cells (NSCs). These processes, mainly characterized in rodents, remain elusive in primates and thus our understanding of conserved and species-specific features. Here, we profiled 761,529 single-cell transcriptomes from multiple regions of the prenatal macaque telencephalon. We defined the molecular programs of the early organizing centers and their cross-talk with NSCs, finding primate-biased signaling active in the antero-ventral telencephalon. Regional transcriptomic divergences were evident at early states of neocortical NSC progression and in differentiated neurons and astrocytes, more than in intermediate transitions. Finally, we show that neuropsychiatric disease- and brain cancer-risk genes have putative early roles in the telencephalic organizers' activity and across cortical NSC progression.

Transcriptomic landscape of mammalian ventral pallidum at single-cell resolution

“…3B), which were largely conserved between the two NHPs and mice. We also observed proportionally fewer neuronal nuclei in both NHP atlases compared to the mouse atlas, consistent with previous reports (38)(39)(40)(41)(42)(43).…”

Multimodal analyses reveal genes driving electrophysiological maturation of neurons in the primate prefrontal cortex

“…At the lowest hierarchical level of cell type classification, we transcriptomically defined 85 cell subtypes (Figure S2E; Table S3). By integrating our dataset with two published snRNA-seq datasets that analyzed early fetal 28 and adult 23 macaque dlPFC, we observed that our data bridges the embryonic/early fetal cell types with the adult cell types, facilitating the tracing of the developmental origins of distinct adult cell subtypes (Figures 1E-1G).…”

“…S2F). By integrating our dataset with two published snRNA-seq datasets that analyzed early fetal (20) and adult (16) macaque dlPFC, we observed that our data bridges the embryonic/early fetal cell types with the adult cell types, thus facilitating future studies focused on tracing the developmental origins of distinct adult cell subtypes (fig. S3).…”

“…S1B and 1C). Using this strategy, together with cell type-specific marker genes and integration with human and macaque single-cell gene expression datasets (9,16,20), we defined 9 cell classes that included glutamatergic excitatory neurons, GABAergic inhibitory neurons, glial progenitor cells (GPC), astrocytes, oligodendrocyte precursor cells (OPC), oligodendrocytes, microglia, vascular leptomeningeal cells (VLMC), endothelial cells (Materials and Methods, fig. S2A).…”

“…After removing batch effects, we used unsupervised clustering to group nuclei into transcriptomically defined groups (Figures S1B-S1C). Using this strategy, together with cell type-specific marker genes 16,23,28 , we defined 9 major cell classes that included glutamatergic excitatory neurons (ExN), GABAergic inhibitory neurons (InN), glial progenitor cells (GPC), astrocytes, oligodendrocyte precursor cells (OPC), oligodendrocytes, microglia, vascular leptomeningeal cells (VLMC), and endothelial cells (Figure S2A). We re-clustered the ExN and InN nuclei to identify their subclasses 1C and S2B-S2C).…”