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

During early telencephalic development, intricate processes of regional patterning and neural stem cell (NSC) fate specification take place. However, our understanding of these processes in primates, including both conserved and species-specific features, remains limited. Here, we profiled 761,529 single-cell transcriptomes from multiple regions of the prenatal macaque telencephalon. We deciphered the molecular programs of the early organizing centers and their cross-talk with NSCs, revealing primatebiased galanin-like peptide (GALP) signaling in the antero-ventral telencephalon. Regional transcriptomic variations were observed along the fronto-temporal axis during early stages of neocortical NSC progression and in neurons and astrocytes. Additionally, we found that genes associated with neuropsychiatric disorders and brain cancer risk might play critical roles in the early telencephalic organizers and during NSC progression. Overall design: Employing timed-pregnant rhesus macaques, we dissected multiple prospective regions of the prenatal telencephalon, from embryonic day (E)37, prior to neurogenesis, up to mid-gliogenesis at E110 (12). Anterior (A)/frontal (FR), dorso-lateral (DL)/putative motor-somatosensory (MS), putative temporal, posterior (P)/occipital (OC) areas, and ganglionic eminence (GE) were recognized at the earliest stages (E37-E78). Then, at the latest stages (E93-E110), we collected the cortical wall of up to 13 regions of the neocortex, including multiple sub-areas from the prefrontal (dorsolateral: DFC; orbital: OFC; medial: MFC; ventrolateral: VFC), primary motor (M1C), parietal (primary somatosensory: S1C; inferior parietal: IPC; posterior cingulate: PCC), insula (Ins), temporal (inferior: ITC; superior: STC; primary auditory: A1C), occipital (primary visual: V1), and three regions from GE (medial: MGE; lateral: LGE; caudal: CGE) (24). Eighty-two samples categorized were processed for scRNA-seq. After stringent quality control, a total of 761,529 high-quality individual cells were obtained.