Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development

Suijuan Zhong (), Mengdi Wang, Luwei Huang, Youqiao Chen, Yuxin Ge, Jiyao Zhang, Yingchao Shi, Hao Dong, Xin Zhou, Bosong Wang, Tian Lu, Xiaoxi Jing, Yufeng Lu, Junjing Zhang, Xiaoqun Wang and Qian Wu ()
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Suijuan Zhong: Beijing Normal University
Mengdi Wang: Chinese Academy of Sciences
Luwei Huang: Chinese Academy of Sciences
Youqiao Chen: Beijing Normal University
Yuxin Ge: Beijing Normal University
Jiyao Zhang: Beijing Normal University
Yingchao Shi: Guangdong Institute of Intelligence Science and Technology
Hao Dong: Chinese Academy of Sciences
Xin Zhou: Beijing Normal University
Bosong Wang: Beijing Normal University
Tian Lu: Chinese Academy of Sciences
Xiaoxi Jing: Beijing Normal University
Yufeng Lu: Chinese Academy of Sciences
Junjing Zhang: Beijing Normal University
Xiaoqun Wang: Beijing Normal University
Qian Wu: Beijing Normal University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Human cerebellar development is orchestrated by molecular regulatory networks to achieve cytoarchitecture and coordinate motor and cognitive functions. Here, we combined single-cell transcriptomics, spatial transcriptomics and single cell chromatin accessibility states to systematically depict an integrative spatiotemporal landscape of human fetal cerebellar development. We revealed that combinations of transcription factors and cis-regulatory elements (CREs) play roles in governing progenitor differentiation and cell fate determination along trajectories in a hierarchical manner, providing a gene expression regulatory map of cell fate and spatial information for these cells. We also illustrated that granule cells located in different regions of the cerebellar cortex showed distinct molecular signatures regulated by different signals during development. Finally, we mapped single-nucleotide polymorphisms (SNPs) of disorders related to cerebellar dysfunction and discovered that several disorder-associated genes showed spatiotemporal and cell type-specific expression patterns only in humans, indicating the cellular basis and possible mechanisms of the pathogenesis of neuropsychiatric disorders.

Date: 2023
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DOI: 10.1038/s41467-023-43568-6

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