Droplet-based transcriptome profiling of individual synapses.
Droplet-based transcriptome profiling of individual synapses.
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基于液滴的单个突触转录组分析。
DOI：
10.1038/s41587-022-01635-1
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发表时间：
2023
影响因子：
46.9
通讯作者：
Zong,Chenghang
中科院分区：
文献类型：
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作者：
Niu,Muchun;Cao,Wenjian;Wang,Yongcheng;Zhu,Qiangyuan;Luo,Jiayi;Wang,Baiping;Zheng,Hui;Weitz,DavidA;Zong,Chenghang
突触是复杂神经回路中调节神经元间信号传递的重要结构，在形态和电生理上表现出相当大的异质性。到目前为止，我们仍然缺乏一种高通量的方法来描述单个突触之间的分子异质性。在本研究中，我们开发了一个基于液滴的单细胞(Sc)总RNA测序平台，称为基于多重退火和拖尾的液滴中定量scRNA-seq，用于单个轴突的转录组谱分析，主要由突触体组成。在小鼠和人脑样本的突触体转录体或‘突触体’的图谱中，我们检测到与神经元亚型相关的突触体之间的亚簇，并描述了突触内发生的转录剪接的图景。我们将突触体谱分析扩展到阿尔茨海默病(AD)小鼠模型中的突触病变，并发现了AD相关突触基因表达的变化，这些变化无法通过单核转录组谱检测到。总体而言，我们的结果表明，该平台提供了一个高通量、单突触体转录组分析工具，将促进未来神经科学的发现。
Synapses are crucial structures that mediate signal transmission between neurons in complex neural circuits and display considerable morphological and electrophysiological heterogeneity. So far we still lack a high-throughput method to profile the molecular heterogeneity among individual synapses. In the present study, we develop a droplet-based single-cell (sc) total-RNA-sequencing platform, called Multiple-Annealing-and-Tailing-based Quantitative scRNA-seq in Droplets, for transcriptome profiling of individual neurites, primarily composed of synaptosomes. In the synaptosome transcriptome, or ‘synaptome’, profiling of both mouse and human brain samples, we detect subclusters among synaptosomes that are associated with neuronal subtypes and characterize the landscape of transcript splicing that occurs within synapses. We extend synaptome profiling to synaptopathy in an Alzheimer’s disease (AD) mouse model and discover AD-associated synaptic gene expression changes that cannot be detected by single-nucleus transcriptome profiling. Overall, our results show that this platform provides a high-throughput, single-synaptosome transcriptome profiling tool that will facilitate future discoveries in neuroscience.