A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex

• Published in: Nature (London) Vol. 555; no. 7697; pp. 524 - 528
• Main Authors: Zhong, Suijuan, Zhang, Shu, Fan, Xiaoying, Wu, Qian, Yan, Liying, Dong, Ji, Zhang, Haofeng, Li, Long, Sun, Le, Pan, Na, Xu, Xiaohui, Tang, Fuchou, Zhang, Jun, Qiao, Jie, Wang, Xiaoqun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.03.2018; Nature Publishing Group
• Subjects: 14/1; 14/19; 45/91; 631/114/2404; 631/378/2571/2573; Bioinformatics; Brain; Brain research; Cell migration; Cells (biology); Cognition & reasoning; Cognitive ability; Data analysis; Data processing; Decision making; Embryogenesis; Embryonic growth stage; Gene expression; Gene sequencing; Genetic aspects; Genomes; Human behavior; Humanities and Social Sciences; letter; Mammals; Memory; Morphology; multidisciplinary; Neural networks; Neural stem cells; Neurodevelopmental disorders; Neurogenesis; Neurons; Ontology; Prefrontal cortex; Progenitor cells; Ribonucleic acid; RNA; RNA sequencing; Science; Social behavior; Trajectory analysis
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature25980

WebAnalysis of gene expression at single-cell resolution in the developing prefrontal cortex of the human embryo reveals a diversity of cell types, elucidates cell lineages and identifies signalling pathways that regulate development. RNA-seq survey of early brain development Advances in single-cell RNA-sequencing technology are making it possible to identify the many different types of cell that participate in the assembly of brain structures. Xiaoqun Wang and colleagues conducted a survey of cell types in the developing human prefrontal cortex (PFC) between gestational ages 8 and 26 weeks. They identified 35 different cell subtypes that emerge during PFC development and tracked their fate trajectories over time. The data provide a molecular and cellular overview of the assembly of the human PFC at early and middle gestational stages. 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 behaviour 1 , 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.