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

灵长类感觉神经元的单细胞转录组学识别与慢性疼痛相关的细胞类型

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作者:Jussi Kupari #, Dmitry Usoskin #, Marc Parisien, Daohua Lou, Yizhou Hu, Michael Fatt, Peter Lönnerberg, Mats Spångberg, Bengt Eriksson, Nikolaos Barkas, Peter V Kharchenko, Karin Loré, Samar Khoury, Luda Diatchenko, Patrik Ernfors

Abstract

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.

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