Projection-TAGs enable multiplex projection tracing and multi-modal profiling of projection neurons
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 o...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60360-w |
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| author | Lite Yang Fang Liu Hannah Hahm Takao Okuda Xiaoyue Li Yufen Zhang Vani Kalyanaraman Monique R. Heitmeier Vijay K. Samineni |
| author_facet | Lite Yang Fang Liu Hannah Hahm Takao Okuda Xiaoyue Li Yufen Zhang Vani Kalyanaraman Monique R. Heitmeier Vijay K. Samineni |
| author_sort | Lite Yang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-208de1f2a1ef417cb413503b2c11c955 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-208de1f2a1ef417cb413503b2c11c9552025-08-20T03:03:25ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-60360-wProjection-TAGs enable multiplex projection tracing and multi-modal profiling of projection neuronsLite Yang0Fang Liu1Hannah Hahm2Takao Okuda3Xiaoyue Li4Yufen Zhang5Vani Kalyanaraman6Monique R. Heitmeier7Vijay K. Samineni8Department of Anesthesiology, Washington University Pain Center, Washington University School of MedicineDepartment of Anesthesiology, Washington University Pain Center, Washington University School of MedicineDepartment of Anesthesiology, Washington University Pain Center, Washington University School of MedicineDepartment of Anesthesiology, Washington University Pain Center, Washington University School of MedicineDepartment of Anesthesiology, Washington University Pain Center, Washington University School of MedicineDepartment of Anesthesiology, Washington University Pain Center, Washington University School of MedicineDepartment of Anesthesiology, Washington University Pain Center, Washington University School of MedicineDepartment of Anesthesiology, Washington University Pain Center, Washington University School of MedicineDepartment of Anesthesiology, Washington University Pain Center, Washington University School of MedicineAbstract 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.https://doi.org/10.1038/s41467-025-60360-w |
| spellingShingle | Lite Yang Fang Liu Hannah Hahm Takao Okuda Xiaoyue Li Yufen Zhang Vani Kalyanaraman Monique R. Heitmeier Vijay K. Samineni Projection-TAGs enable multiplex projection tracing and multi-modal profiling of projection neurons Nature Communications |
| title | Projection-TAGs enable multiplex projection tracing and multi-modal profiling of projection neurons |
| title_full | Projection-TAGs enable multiplex projection tracing and multi-modal profiling of projection neurons |
| title_fullStr | Projection-TAGs enable multiplex projection tracing and multi-modal profiling of projection neurons |
| title_full_unstemmed | Projection-TAGs enable multiplex projection tracing and multi-modal profiling of projection neurons |
| title_short | Projection-TAGs enable multiplex projection tracing and multi-modal profiling of projection neurons |
| title_sort | projection tags enable multiplex projection tracing and multi modal profiling of projection neurons |
| url | https://doi.org/10.1038/s41467-025-60360-w |
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