Projection-TAGs enable multiplex projection tracing and multi-modal profiling of projection neurons

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• Single-cell multiomic techniques are crucial for mapping neuronal cell types and their projections.
• Current tools lack efficiency for studying the complex wiring, spatial organization, and molecular landscapes of projection neurons.

Purpose of the Study:

• To introduce Projection-TAGs, a novel retrograde adeno-associated virus (AAV) platform.
• To enable multiplex tagging and profiling of projection neurons for comprehensive brain mapping.

Main Methods:

• Developed Projection-TAGs, a retrograde AAV platform utilizing RNA barcodes for multiplex tagging.
• Applied Projection-TAGs for multiplex projection tracing in the cortex.
• Conducted high-throughput single-cell profiling of transcriptional and epigenetic landscapes in cortical projection neurons from female mice.

Main Results:

• Successfully demonstrated multiplex projection tracing of cortical neurons.
• Characterized the transcriptional and epigenetic landscapes of these neurons.
• Showcased the ability to capture activity-dependent neuronal recruitment and molecular features.

Conclusions:

• Projection-TAGs provide a flexible, usable, and compatible tool for neuroscience research.
• This platform facilitates the construction of a comprehensive multi-modal map of brain neuronal cell types and their projections.
• Enables snapshot analysis of activity-dependent neuronal populations and their molecular characteristics.