BioProject

The cellular and genetic mechanism underlying the human-specific features of cortex development remains unclear. More...

The cellular and genetic mechanism underlying the human-specific features of cortex development remains unclear. We generated a cell-type resolved atlas of transcriptome and chromatin accessibility of the developing macaque and mouse prefrontal cortex, and conducted evolutionary analyses with the published complementary human data. The cortex cell type composition shows an overall conservation across species. We found the human neural progenitors show extensive transcriptional rewiring in the growth factor and extracellular matrix pathways. Expression of the human-specific progenitor marker ITGA2 in the cortex of fetal mouse promotes progenitor proliferation and an increased upper-layer neuron proportion. We demonstrate that these transcriptional divergences are primarily driven by the activity changes of the distal regulatory elements in the genome. Markedly, the chromatin regions with human-gained accessibility enrich the 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. Overall design: To investigate the cellular and genetic mechanism of the human specifications in cortex development, We generated a comprehensive cell atlas of transcriptome and regulatome for macaque and mouse prefrontal cortex (PFC) during mid-digestion using snRNA-seq, scATAC-seq and scMultiome. Less...