The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour1,2. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex. However, it is still difficult to identify cell types in the developing human prefrontal cortex and to distinguish their developmental features. Here we analyse more than 2,300 single cells in the developing human prefrontal cortex from gestational weeks 8 to 26 using RNA sequencing. We identify 35 subtypes of cells in six main classes and trace the developmental trajectories of these cells. Detailed analysis of neural progenitor cells highlights new marker genes and unique developmental features of intermediate progenitor cells. We also map the timeline of neurogenesis of excitatory neurons in the prefrontal cortex and detect the presence of interneuron progenitors in early developing prefrontal cortex. Moreover, we reveal the intrinsic development-dependent signals that regulate neuron generation and circuit formation using single-cell transcriptomic data analysis. Our screening and characterization approach provides a blueprint for understanding the development of the human prefrontal cortex in the early and mid-gestational stages in order to systematically dissect the cellular basis and molecular regulation of prefrontal cortex function in humans.
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Gene Expression Omnibus
We thank members of the Wang and Tang laboratories for discussions. This work was supported by National Basic Research Program of China (2014CB964600), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020601), the National Natural Science Foundation of China (NSFC) (91732301, 31371100, 31771140), National Key Research and Development Program of China (2017YFA0103303, 2017YFA0102601), Shanghai Brain-Intelligence Project from STCSM (16JC1420500), Newton Advanced Fellowship (NA140246) to X.W. and Youth Innovation Promotion Association CAS to Q.W.
Extended data figures
This file contains supplementary table 1 - gene list of different cells types and comparison. The spreadsheets include marker genes of all 6 major cell types, specific genes of the sub-clusters within each cell type, excitatory neuron markers of different weeks and gestational stages.
About this article
Nature Neuroscience (2018)