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. One-Sentence Summary Single-cell transcriptomics reveals molecular logics of arealization and neural stem cell fate specification in developing macaque brain