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

被引:113
作者
Kupari, Jussi [1 ]
Usoskin, Dmitry [1 ]
Parisien, Marc [2 ]
Lou, Daohua [1 ]
Hu, Yizhou [1 ]
Fatt, Michael [1 ]
Lonnerberg, Peter [1 ]
Spangberg, Mats [3 ]
Eriksson, Bengt [3 ]
Barkas, Nikolaos [4 ]
Kharchenko, Peter V. [4 ]
Lore, Karin [5 ,6 ]
Khoury, Samar [2 ]
Diatchenko, Luda [2 ]
Ernfors, Patrik [1 ]
机构
[1] Karolinska Inst, Dept Med Biochem & Biophys, Div Mol Neurobiol, Stockholm, Sweden
[2] McGill Univ, Alan Edwards Ctr Res Pain, Dept Anesthesia, Sch Med,Sch Dent, Montreal, PQ, Canada
[3] Karolinska Inst, Astrid Fagraeus Lab, Comparat Med, Stockholm, Sweden
[4] Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA
[5] Karolinska Inst, Div Immunol & Allergy, Stockholm, Sweden
[6] Karolinska Inst, Ctr Mol Med, Stockholm, Sweden
基金
英国惠康基金;
关键词
ROOT GANGLION NEURONS; CONGENITAL INSENSITIVITY; GENE-EXPRESSION; RESPONSES; ITCH; SUBPOPULATION; ARCHITECTURE; SENSITIVITY; EXPERIENCE; MUTATIONS;
D O I
10.1038/s41467-021-21725-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:15
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