Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain

• Published in: Nature communications Vol. 12; no. 1; p. 1510
• Main Authors: Kupari, Jussi, Usoskin, Dmitry, Parisien, Marc, Lou, Daohua, Hu, Yizhou, Fatt, Michael, Lönnerberg, Peter, Spångberg, Mats, Eriksson, Bengt, Barkas, Nikolaos, Kharchenko, Peter V., Loré, Karin, Khoury, Samar, Diatchenko, Luda, Ernfors, Patrik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 14/32; 38/43; 38/91; 49/39; 631/337/2019; 631/378/1959/2605; 631/378/2620/410/2610; 692/308/2056; Animals; Chronic pain; Chronic Pain - genetics; Chronic Pain - metabolism; Convergence; Dorsal root ganglia; Female; Ganglia, Spinal; Gene Expression; Genomes; Heritability; Humanities and Social Sciences; Humans; Learning algorithms; Macaca mulatta; Machine learning; Male; Medicin och hälsovetenskap; Mice; multidisciplinary; Neurons; Pain; Primates; Science; Science (multidisciplinary); Sensory neurons; Sensory Receptor Cells - metabolism; Transcriptome; Transcriptomes; Uniqueness; Wildlife conservation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21725-z

Distinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain. However, molecular insights into the primate sensory neurons are missing. Here we classify non-human primate dorsal root ganglion sensory neurons based on their transcriptome and map human pain heritability to neuronal types. First, we identified cell correlates between two major datasets for mouse sensory neuron types. Machine learning exposes an overall cross-species conservation of somatosensory neurons between primate and mouse, although with differences at individual gene level, highlighting the importance of primate data for clinical translation. We map genomic loci associated with chronic pain in human onto primate sensory neuron types to identify the cellular origin of chronic pain. Genome-wide associations for chronic pain converge on two different neuronal types distributed between pain disorders that display different genetic susceptibilities, suggesting both unique and shared mechanisms between different pain conditions. The contribution of distinct types of dorsal root ganglion neurons to chronic pain is unclear. Here, the authors molecularly profile non-human primate sensory neurons and show that genome-wide associations converge on two neuronal types with different genetic susceptibilities for chronic pain.