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07, 2018;28 (7): 730-745.

Spatial transcriptomic survey of human embryonic cerebral cortex by single-cell RNA-seq analysis.

Xiaoying Fan, Ji Dong, Suijuan Zhong, Yuan Wei, Qian Wu, Liying Yan, Jun Yong, Le Sun, Xiaoye Wang, Yangyu Zhao, Wei Wang, Jie Yan, Xiaoqun Wang, Jie Qiao, Fuchou Tang
Author Information
  1. Xiaoying Fan: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China.
  2. Ji Dong: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China.
  3. Suijuan Zhong: State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology; Institute of Brain-Intelligence Science and Technology Zhangjiang Laboratory (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  4. Yuan Wei: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China.
  5. Qian Wu: State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology; Institute of Brain-Intelligence Science and Technology Zhangjiang Laboratory (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  6. Liying Yan: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China.
  7. Jun Yong: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China.
  8. Le Sun: State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology; Institute of Brain-Intelligence Science and Technology Zhangjiang Laboratory (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  9. Xiaoye Wang: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China.
  10. Yangyu Zhao: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China.
  11. Wei Wang: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China.
  12. Jie Yan: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China.
  13. Xiaoqun Wang: State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology; Institute of Brain-Intelligence Science and Technology Zhangjiang Laboratory (Shanghai), Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. xiaoqunwang@ibp.ac.cn.
  14. Jie Qiao: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China. jie.qiao@263.net. ORCID
  15. Fuchou Tang: Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, 100871, China. tangfuchou@pku.edu.cn. ORCID
PMID: 29867213 DOI: 10.1038/s41422-018-0053-3

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.

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MeSH Term

Astrocytes
Base Sequence
Cerebral Cortex
Embryonic Development
Female
Gene Expression Profiling
Humans
Male
Nervous System Diseases
Neurogenesis
Neurons
Pregnancy
Pregnancy Trimester, Second
Sequence Analysis, RNA
Single-Cell Analysis
Journal Article Research Support, Non-U.S. Gov't

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