Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development

Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development. Here, we have searched for such differences by analysing cerebral organoids from human and chimpanzees using immunohistochemistry, live imaging, and single-cell transcriptomics. We find that the cytoarchitecture, cell type composition, and neurogenic gene expression programs of humans and chimpanzees are remarkably similar. Notably, however, live imaging of apical progenitor mitosis uncovered a lengthening of prometaphase-metaphase in humans compared to chimpanzees that is specific to proliferating progenitors and not observed in non-neural cells. Consistent with this, the small set of genes more highly expressed in human apical progenitors points to increased proliferative capacity, and the proportion of neurogenic basal progenitors is lower in humans. These subtle differences in cortical progenitors between humans and chimpanzees may have consequences for human neocortex evolution. Overall design: Single-cell transcriptomes from human and chimpanzee cerebral organoids from multiple time points were analyzed in this study. All single cell samples were processed on the microfluidic Fluidigm C1 platform and contain 92 external RNA spike-ins. Human data were generated from dissociated whole organoids derived from induced pluripotent stem cell line SC102-A1 (iPSC SC102-A1) at 60 days after the start of embryoid body culture. Chimpanzee data were generated from dissociated whole organoids from iPS cell line SandraA at 45 days and PR818-5 at 50 days, 55 days, 61 days and 80 days and microdissected cortical-like regions from chimpanzee iPS cell line PR818-5 at 51 days and 62 days.