Spatiotemporal transcriptome atlas reveals the regional specification of the developing human brain

Yanxin Li; Zhongqiu Li; Changliang Wang; Min Yang; Ziqing He; Feiyang Wang; Yuehong Zhang; Rong Li; Yunxia Gong; Binhong Wang; Baoguang Fan; Chunyue Wang; Lei Chen; Hong Li; Peifu Shi; Nana Wang; Zhifeng Wei; Yan-Ling Wang; Lei Jin; Peng Du; Ji Dong; Jianwei Jiao

doi:10.1016/j.cell.2023.11.016

Spatiotemporal transcriptome atlas reveals the regional specification of the developing human brain

Cell. 2023 Dec 21;186(26):5892-5909.e22. doi: 10.1016/j.cell.2023.11.016. Epub 2023 Dec 12.

Authors

Yanxin Li¹, Zhongqiu Li¹, Changliang Wang², Min Yang³, Ziqing He⁴, Feiyang Wang¹, Yuehong Zhang⁵, Rong Li⁶, Yunxia Gong⁵, Binhong Wang⁵, Baoguang Fan⁵, Chunyue Wang⁵, Lei Chen⁷, Hong Li¹, Peifu Shi⁸, Nana Wang⁸, Zhifeng Wei⁸, Yan-Ling Wang¹, Lei Jin⁹, Peng Du¹⁰, Ji Dong¹¹, Jianwei Jiao¹²

Affiliations

¹ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
² GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou 510799, China.
³ MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.
⁴ GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou 510799, China; Faculty of Health Sciences University of Macau, Macau 999078, China.
⁵ Tongzhou Maternal and Child Health Hospital of Beijing, Beijing 101100, China.
⁶ Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Department of Obstetrics and Gynecology, Ministry of Education, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China; National Clinical Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
⁷ Six Medical Center, Chinese PLA General Hospital, Beijing 100048, China.
⁸ Annoroad Gene Technology, Beijing 100176, China.
⁹ Institute of Reproductive and Child Health, Peking University, National Health Commission Key Laboratory, Peking University, Beijing 100191, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China. Electronic address: jinlei@bjmu.edu.cn.
¹⁰ MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address: pengdu@pku.edu.cn.
¹¹ GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou 510799, China. Electronic address: dong_ji@gzlab.ac.cn.
¹² State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: jwjiao@ioz.ac.cn.

PMID: 38091994
DOI: 10.1016/j.cell.2023.11.016

Abstract

Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6-23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain.

Keywords: human brain development; multiple brain regions of the developing human brain; regional heterogeneity; scRNA-seq; scStereo-seq; spatial transcriptomics.

Publication types

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

MeSH terms

Brain* / growth & development
Brain* / metabolism
Dopaminergic Neurons
GABAergic Neurons
Humans
Mesencephalon
Neocortex
Transcriptome*