Leveraging deep single-soma RNA sequencing to explore the neural basis of human somatosensation
The versatility of somatosensation arises from heterogeneous dorsal root ganglion (DRG) neurons. However, soma transcriptomes of individual human (h)DRG neurons-critical information to decipher their functions-are lacking due to technical difficulties. In this study, we isolated somata from individual hDRG neurons and conducted deep RNA sequencing (RNA-seq) to detect, on average, over 9,000 unique genes per neuron, and we identified 16 neuronal types. These results were corroborated and validated by spatial transcriptomics and RNAscope in situ hybridization. Cross-species analyses revealed divergence among potential pain-sensing neurons and the likely existence of human-specific neuronal types. Molecular-profile-informed microneurography recordings revealed temperature-sensing properties across human sensory afferent types. In summary, by employing single-soma deep RNA-seq and spatial transcriptomics, we generated an hDRG neuron atlas, which provides insights into human somatosensory physiology and serves as a foundation for translational work.
Authors
- Mingyao Li (ORCID: https://orcid.org/0000-0003-2422-9494)
- Saad S. Nagi (ORCID: https://orcid.org/0000-0001-8773-8232)
- Patrik Ernfors (ORCID: https://orcid.org/0000-0002-1140-3986)
- Guo‐li Ming (ORCID: https://orcid.org/0000-0002-2517-6075)
- Hao Wu (ORCID: https://orcid.org/0000-0003-4395-6929)
- Hongjun Song (ORCID: https://orcid.org/0000-0002-8720-5310)
- Suna Li Cranfill (ORCID: https://orcid.org/0000-0002-3431-0061)
- You Lu (ORCID: https://orcid.org/0000-0002-0075-8167)
- Frank L. Rice (ORCID: https://orcid.org/0000-0003-4676-4252)
- Hanying Yan (ORCID: https://orcid.org/0000-0002-9227-1742)
- Minghong Ma (ORCID: https://orcid.org/0000-0002-5027-9623)
- Huasheng Yu (ORCID: https://orcid.org/0000-0001-5641-2512)
- Yijing Su (ORCID: https://orcid.org/0000-0002-4146-0068)
- Wenqin Luo (ORCID: https://orcid.org/0000-0002-2486-807X)
- Mayank Gautam (ORCID: https://orcid.org/0000-0002-7257-5837)
- Jussi Kupari (ORCID: https://orcid.org/0000-0003-1540-5193)
- Håkan Olausson (ORCID: https://orcid.org/0000-0002-6319-1786)
- Dmitry Usoskin (ORCID: https://orcid.org/0000-0001-9122-6387)
- Otmane Bouchatta (ORCID: https://orcid.org/0000-0002-1639-0600)
- John T. Seykora (ORCID: https://orcid.org/0000-0003-0383-031X)
- Stephen M. Prouty (ORCID: https://orcid.org/0000-0001-9436-8268)
- Phillip J. Albrecht (ORCID: https://orcid.org/0000-0002-9677-0442)
- James P. Wymer (ORCID: https://orcid.org/0000-0003-0809-2977)
- Andrew G. Marshall (ORCID: https://orcid.org/0000-0001-8273-7089)
- Yizhou Hu (ORCID: https://orcid.org/0000-0002-2635-0258)
- Max Glanz
Institutions
- Linköping University (SE)
- University of Liverpool (GB)
- Karolinska Institutet (SE)
- University of Florida (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Neuroscience
- Published
- 2024-11-04
- DOI
- https://doi.org/10.1038/s41593-024-01794-1
- Citations
- 60
- Primary Topic
- Neurobiology and Insect Physiology Research
- Type
- article
- Field-Weighted Citation Impact
- 16.10
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Sveriges Läkarförbund
- National Eye Institute
- National Institute of Neurological Disorders and Stroke
- National Institute of Dental and Craniofacial Research