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Droplet-based transcriptome profiling of individual synapses.

Muchun Niu1,2, Wenjian Cao1,3,4, Yongcheng Wang5,6,7

  • 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Nature Biotechnology
|January 16, 2023
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel droplet-based sequencing method to profile the molecular makeup of individual synapses. This new tool, called synaptome profiling, reveals synapse subtypes and gene expression changes in Alzheimer's disease.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genomics

Background:

  • Synapses are vital for neural communication and exhibit significant heterogeneity.
  • Existing methods lack high-throughput capabilities for profiling molecular diversity at the single-synapse level.

Purpose of the Study:

  • To develop a high-throughput platform for transcriptome profiling of individual synapses.
  • To characterize the molecular landscape and heterogeneity of synaptomes.
  • To investigate synaptic gene expression changes in Alzheimer's disease.

Main Methods:

  • Development of a droplet-based single-cell (sc) total-RNA-sequencing platform (Multiple-Annealing-and-Tailing-based Quantitative scRNA-seq in Droplets).
  • Application of the platform for transcriptome profiling of individual neurites (synaptomes) from mouse and human brain samples.
  • Extension of the method to analyze synaptopathy in an Alzheimer's disease mouse model.

Main Results:

  • The platform successfully profiled the 'synaptome' (synaptosome transcriptome) from mouse and human samples.
  • Identified synaptosome subclusters associated with specific neuronal subtypes.
  • Characterized transcript splicing within synapses.
  • Discovered Alzheimer's disease-associated synaptic gene expression changes missed by single-nucleus methods.

Conclusions:

  • The developed platform offers high-throughput, single-synaptosome transcriptome profiling.
  • This tool enables detailed molecular characterization of synapse heterogeneity.
  • Synaptome profiling is a powerful approach for studying neurological disorders like Alzheimer's disease.