The single-cell and spatial transcriptional landscape of human gastrulation and early brain development

Bo Zeng; Zeyuan Liu; Yufeng Lu; Suijuan Zhong; Shenyue Qin; Luwei Huang; Yang Zeng; Zixiao Li; Hao Dong; Yingchao Shi; Jialei Yang; Yalun Dai; Qiang Ma; Le Sun; Lihong Bian; Dan Han; Youqiao Chen; Xin Qiu; Wei Wang; Oscar Marín; Qian Wu; Yongjun Wang; Xiaoqun Wang

doi:10.1016/j.stem.2023.04.016

The single-cell and spatial transcriptional landscape of human gastrulation and early brain development

Cell Stem Cell. 2023 Jun 1;30(6):851-866.e7. doi: 10.1016/j.stem.2023.04.016. Epub 2023 May 15.

Authors

Bo Zeng¹, Zeyuan Liu¹, Yufeng Lu², Suijuan Zhong¹, Shenyue Qin³, Luwei Huang⁴, Yang Zeng⁵, Zixiao Li⁶, Hao Dong⁴, Yingchao Shi⁷, Jialei Yang⁸, Yalun Dai⁸, Qiang Ma⁴, Le Sun⁹, Lihong Bian¹⁰, Dan Han¹¹, Youqiao Chen¹², Xin Qiu⁸, Wei Wang², Oscar Marín¹³, Qian Wu¹⁴, Yongjun Wang¹⁵, Xiaoqun Wang¹⁶

Affiliations

¹ State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China; Changping Laboratory, Beijing 102206, China.
² State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
³ Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK.
⁴ State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ State Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China.
⁶ China National Clinical Research Center for Neurological Diseases, Beijing 100070, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University & Capital Medical University, Beijing 100069, China.
⁷ State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Guangdong Institute of Intelligence Science and Technology, Guangdong 519031, China.
⁸ China National Clinical Research Center for Neurological Diseases, Beijing 100070, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
⁹ Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100069, China.
¹⁰ Department of Gynecology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China.
¹¹ Department of Obstetrics & Gynecology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
¹² State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
¹³ Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK. Electronic address: oscar.marin@kcl.ac.uk.
¹⁴ State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China; Changping Laboratory, Beijing 102206, China. Electronic address: qianwu@bnu.edu.cn.
¹⁵ China National Clinical Research Center for Neurological Diseases, Beijing 100070, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University & Capital Medical University, Beijing 100069, China. Electronic address: yongjunwang@ncrcnd.org.cn.
¹⁶ State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China; State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100069, China; Guangdong Institute of Intelligence Science and Technology, Guangdong 519031, China; Changping Laboratory, Beijing 102206, China; New Cornerstone Science Laboratory, Beijing Normal University, Beijing 100875, China. Electronic address: xiaoqunwang@bnu.edu.cn.

Abstract

The emergence of the three germ layers and the lineage-specific precursor cells orchestrating organogenesis represent fundamental milestones during early embryonic development. We analyzed the transcriptional profiles of over 400,000 cells from 14 human samples collected from post-conceptional weeks (PCW) 3 to 12 to delineate the dynamic molecular and cellular landscape of early gastrulation and nervous system development. We described the diversification of cell types, the spatial patterning of neural tube cells, and the signaling pathways likely involved in transforming epiblast cells into neuroepithelial cells and then into radial glia. We resolved 24 clusters of radial glial cells along the neural tube and outlined differentiation trajectories for the main classes of neurons. Lastly, we identified conserved and distinctive features across species by comparing early embryonic single-cell transcriptomic profiles between humans and mice. This comprehensive atlas sheds light on the molecular mechanisms underlying gastrulation and early human brain development.

Keywords: brain evolution; germ layer differentiation; human gastrulation; nervous system development; neuroepithelial cells; radial glia; single-cell RNA sequencing; spatial transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain
Cell Differentiation
Gastrulation* / genetics
Germ Layers*
Humans
Mice
Organogenesis