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J Mol Cell Biol. 2019 Jan 25. doi: 10.1093/jmcb/mjy089. [Epub ahead of print]

Single-cell transcriptomes reveal molecular specializations of neuronal cell types in the developing cerebellum.

Peng J1,2, Sheng AL1, Xiao Q1,2, Shen L1, Ju XC1, Zhang M1, He ST1,2, Wu C1,2,3, Luo ZG1,2,3,4.

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Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
ShanghaiTech University, Shanghai, China.
Co-innovation Center of Neuroregeneration, Nantong University, Jiangsu Sheng, China.


The cerebellum is critical for controlling motor and non-motor functions via cerebellar circuit that is composed of defined cell types, which approximately account for more than half of neurons in mammals. The molecular mechanisms controlling developmental progression and maturation processes of various cerebellar cell types need systematic investigation. Here, we analyzed transcriptome profiles of 21119 single cells of the postnatal mouse cerebellum and identified eight main cell clusters. Functional annotation of differentially expressed genes revealed trajectory hierarchies of granule cells (GCs) at various states and implied roles of mitochondrion and ATPases in the maturation of Purkinje cells (PCs), the sole output cells of the cerebellar cortex. Furthermore, we analyzed gene expression patterns and co-expression networks of 28 ataxia risk genes, and found that most of them are related with biological process of mitochondrion and around half of them are enriched in PCs. Our results also suggested core transcription factors that are correlated with interneuron differentiation and characteristics for the expression of secretory proteins in glia cells, which may participate in neuronal modulation. Thus, this study presents a systematic landscape of cerebellar gene expression in defined cell types and a general gene expression framework for cerebellar development and dysfunction.


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