Droplet-based transcriptome profiling of individual synapses

• Published in: Nature biotechnology Vol. 41; no. 9; pp. 1332 - 1344
• Main Authors: Niu, Muchun, Cao, Wenjian, Wang, Yongcheng, Zhu, Qiangyuan, Luo, Jiayi, Wang, Baiping, Zheng, Hui, Weitz, David A., Zong, Chenghang
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-09-2023; Nature Publishing Group
• Subjects: 631/1647/2017; 631/61/514/1949; Agriculture; Alzheimer's disease; Axons; Bioinformatics; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Droplets; Gene expression; Gene sequencing; Heterogeneity; Life Sciences; Nervous system; Neural networks; Neurodegenerative diseases; Signal transmission; Synapses; Synaptosomes; Transcriptomes
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/s41587-022-01635-1

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.
High-throughput profiling of the transcriptomes of individual synapses shows molecular heterogeneity.