The cellular and genetic mechanism driving the human-specific developmental changes remains unclear. We generated a cell-type resolved atlas of transcriptome and regulome of the developing macaque and mouse prefrontal cortex, and conducted evolutionary analyses by including the published single-cell human cortex data. We discovered the primate-specific expansion of two neural progenitor subclasses, glia-committed radial glia (RG) and truncated RG. Specifically, the human neural progenitors show extensive transcriptional rewiring, likely regulated by growth factors and the extracellular matrix pathway. Expression of the human-specific progenitor marker ITGA2 in fetal mouse promotes progenitor proliferation. We demonstrate that these transcription divergences are primarily driven by activity changes in the distal regulatory elements. Markedly, the chromatin regions with human-gained accessibility enrich human-fixed sequence changes, as well as sequence polymorphisms associated with intelligence and neuropsychiatric disorders. Our results uncover evolutionary innovations in neural progenitors and gene regulatory mechanism during primate cortex evolution.
Here, we provide the code used to do the integrative analysis of single-cell omics data from fetal neocortex across species.