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Papers of the Week


Papers: 28 June 2025 - 3 July 2025


2025 Jul 1


Nat Commun


40593543


16


1

Editor's Pick

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

Authors

Yang L, Liu F, Hahm H, Okuda T, Li X, Zhang Y, Kalyanaraman V, Heitmeier MR, Samineni VK.

Abstract

Single-cell multiomic techniques have sparked immense interest in developing a comprehensive multi-modal map of diverse neuronal cell types and their brain-wide projections. However, investigating the complex wiring diagram, spatial organization, transcriptional, and epigenetic landscapes of brain-wide projection neurons is hampered by the lack of efficient and easily adoptable tools. Here we introduce Projection-TAGs, a retrograde AAV platform that allows multiplex tagging of projection neurons using RNA barcodes. By using Projection-TAGs, we performed multiplex projection tracing of the cortex and high-throughput single-cell profiling of the transcriptional and epigenetic landscapes of the cortical projection neurons in female mice. Projection-TAGs can be leveraged to obtain a snapshot of activity-dependent recruitment of distinct projection neurons and their molecular features in the context of a specific stimulus. Given its flexibility, usability, and compatibility, we envision that Projection-TAGs can be readily applied to build a comprehensive multi-modal map of brain neuronal cell types and their projections.