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Nature. 2018 Mar 22;555(7697):524-528. doi: 10.1038/nature25980. Epub 2018 Mar 14.

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

Zhong S1,2, Zhang S3, Fan X3, Wu Q1,2, Yan L3, Dong J3, Zhang H4, Li L1,2, Sun L1, Pan N1, Xu X4, Tang F3,5,6, Zhang J4, Qiao J3,5,6, Wang X1,2,7.

Author information

State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing, 100871, China.
Obstetrics and Gynecology, Medical Center of Severe Cardiovascular of Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
Biomedical Institute for Pioneering Investigation via Convergence and Center for Reproductive Medicine, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing, 100871, China.
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
Beijing Institute for Brain Disorders, Beijing, 100069, China.


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. 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.

[Indexed for MEDLINE]

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