Single-Cell Sequencing of the Developing Human Brain
nemo:std-k4axiyp · Short name: kriegstein_sc_10x_proj
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"The human brain is composed of diverse cell types across brain regions that enable unique capabilities. Within the brain, the cerebral cortex is responsible for a number of cognitive functions and sensory integration, with distinct cortical regions controlling a variety of tasks including motion, vision, speech, and judgment. Recent work exploring the cell types of two distinct cortical regions in the human and mouse suggests that excitatory neurons are area specific and emerge during developmental stages of peak neurogenesis. However, further characterization of cortical arealization is required to understand whether gradients, sharp boundaries, or some combination of patterns describes the areal distribution of neurons and other cortical cell types. Importantly, accurate modeling of cortical development and understanding biological constraints for any attempts at stem cell therapies requires characterizing when neuroepithelia or radial glia transition from a uniform population into areal specific progenitors, and the degree to which they are committed to an areal fate. In order to comprehensively characterize the areal diversity of cell types during human development, we performed single-cell sequencing of a variety of cortical regions and sub-cortical structures from 20 intact first and second trimester brain samples. With over a million cells, we identify hundreds of cells types including temporal and area specific neurons, interneurons and radial glia populations, as well as a number of subtypes from each of these classes that are expressed across most cortical areas. Additionally, we find a small number of subpopulations of neuroepithelial cells and identify several key pathways that may regulate the switch from neuroepithelia to radial glia identity. Together, these datasets suggest a model of both area restricted progenitor populations as well as radial glia cell types that are observed across cortical regions, suggesting an orchestrated interplay of fate determination that gives rise to the required cell diversity of the human cerebral cortex."
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