Abstract
The cellular complexity of human brain development has been intensively investigated, although a regional characterization of the entire human cerebral cortex based on single-cell transcriptome analysis has not been reported. Here, we performed RNA-seq on over 4,000 individual cells from 22 brain regions of human mid-gestation embryos. We identified 29 cell sub-clusters, which showed different proportions in each region and the pons showed especially high percentage of astrocytes. Embryonic neurons were not as diverse as adult neurons, although they possessed important features of their destinies in adults. Neuron development was unsynchronized in the cerebral cortex, as dorsal regions appeared to be more mature than ventral regions at this stage. Region-specific genes were comprehensively identified in each neuronal sub-cluster, and a large proportion of these genes were neural disease related. Our results present a systematic landscape of the regionalized gene expression and neuron maturation of the human cerebral cortex.
Highlights
The adult brain of vertebrate animals has extensive capabilities due to its astonishing cell type diversity[1,2] and precise arrangement of regional structures,[3] especially in the cerebral cortex as it is the most evolved organ with the most complex functions in human
As we investigated the transcriptome of the whole cortex at this gestation stage at single-cell resolution, we further analyzed the expression patterns of the high-confidence autism spectrum disorder genes and probable ASD genes.[50]
In this study, we uncovered 29 cell sub-clusters within the midgestation stage of human embryonic cerebral cortex in vivo and identified the unique signature of each type of cell related to their biological functions, such as in the cell cycle, transcription factors (TFs) networks, and metabolism
Summary
The adult brain of vertebrate animals has extensive capabilities due to its astonishing cell type diversity[1,2] and precise arrangement of regional structures,[3] especially in the cerebral cortex as it is the most evolved organ with the most complex functions in human. Neurons located in different cortical layers and regions project to their specific destinations where they can receive and release signals by transmitting neurotransmitters to feel and control.[5,6,7] Previous classifications for neurons were mainly based on their morphological, chemical, and electrical properties. As these properties are controlled genetically, neuron sub-cluster classifications have been defined by distinct molecular characteristics in recent studies.[8,9,10,11,12]
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