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.

中文翻译：

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单细胞转录组揭示了发育中的小脑中神经元细胞类型的分子专长。

小脑对于通过小脑回路控制运动和非运动功能至关重要，小脑回路由定义的细胞类型组成，大约占哺乳动物神经元的一半以上。控制各种小脑细胞类型的发育进程和成熟过程的分子机制需要系统研究。在这里，我们分析了出生后小鼠小脑的21119个单细胞的转录组概况，并确定了8个主要细胞簇。差异表达基因的功能注释揭示了处于不同状态的颗粒细胞（GC）的轨迹层次，并暗示了线粒体和ATP酶在小脑皮层的唯一输出细胞Purkinje细胞（PC）的成熟中的作用。此外，我们分析了28个共济失调风险基因的基因表达模式和共表达网络，发现它们大多数与线粒体的生物学过程有关，其中约一半富含PCs。我们的研究结果还表明，与神经元间分化和神经胶质细胞分泌蛋白表达特征相关的核心转录因子可能参与神经元调节。因此，这项研究提出了定义的细胞类型中小脑基因表达的系统性景观和小脑发育和功能障碍的通用基因表达框架。我们的研究结果还表明，与神经元间分化和神经胶质细胞分泌蛋白表达特征相关的核心转录因子可能参与神经元调节。因此，这项研究提出了定义的细胞类型中小脑基因表达的系统性景观和小脑发育和功能障碍的通用基因表达框架。我们的研究结果还表明，与神经元间分化和神经胶质细胞分泌蛋白表达特征相关的核心转录因子可能参与神经元调节。因此，这项研究提出了定义的细胞类型中小脑基因表达的系统性景观和小脑发育和功能障碍的通用基因表达框架。