High resolution single-cell atlas of early human brain development

The human brain is formed through a highly regulated and extremely complex process. Although the principles of brain development are similar in other mammals, studies of model organisms such as rodents cannot reveal human-specific mechanisms in the brain. In this study, we performed single-cell RNA-sequencing of more than 1.5 million cells from all brain regions at 5 – 14 post-conceptional weeks. We also used 448-plex RNA in situ hybridization at 5 weeks post-conception to map the precise spatial anatomical domains of corresponding transcriptomic subtypes. The detailed resolution of this dataset allowed us to characterize general principles of brain development as well as delineate the differentiation trajectories of several brain regions. In the cortex, we identified three different ongoing molecular programs during development: the cell cycle, differentiation, and maturation. We found that differentiation is coupled to cell cycle progression in cortical progenitors. Moreover, we uncovered region-specificity among arising glial populations maturing into distinct pre-astrocytes and pre-oligodendrocyte precursor cells (pre-OPCs). Our findings reveal the emergence of cell types during the first trimester of human brain development and provide a comprehensive reference for probing the cellular basis of human neurodevelopment and neurological diseases.