美国贝勒医学院Chenghang Zong和哈佛大学David A. Weitz团队合作在研究中取得进展。他们开发出基于水滴的单个突触转录组分析方法。这一研究成果于2023年1月16日发表在国际学术期刊《自然—生物技术》上。

研究人员研发了一种基于液滴的单细胞（sc）总RNA测序平台，称为液滴中基于多重退火和拖尾的定量scRNA-seq，主要对由突触体组成的单个神经突进行转录组分析。在突触体转录组或“突触组”对小鼠和人脑样本进行分析，研究人员检测到与神经元亚型相关突触体的亚簇，并揭示了突触内发生的转录本剪接情形。研究人员将突触组谱应用到阿尔茨海默病（AD）小鼠模型的突触中，发现了单核转录组谱无法检测到的AD相关突触基因表达变化。总体而言，该结果表明这个平台提供了一种高通量、单突触体转录组分析工具，将促进神经科学的发现。

研究人员表示，突触是介导复杂神经回路中神经元之间信号传递的关键结构，具有多变的形态和电生理异质性。到目前为止，仍然缺乏一种高通量方法来分析单个突触之间的分子异质性。

附：英文原文

Title: Droplet-based transcriptome profiling of individual synapses

Author: Niu, Muchun, Cao, Wenjian, Wang, Yongcheng, Zhu, Qiangyuan, Luo, Jiayi, Wang, Baiping, Zheng, Hui, Weitz, David A., Zong, Chenghang

Issue&Volume: 2023-01-16

Abstract: 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.

DOI: 10.1038/s41587-022-01635-1

Source: https://www.nature.com/articles/s41587-022-01635-1