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Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain [SmartSeq2]

ABSTRACT: Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain [SmartSeq2]

PROVIDER: PRJNA694961 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13532600.fastq.gz	Fastqsanger.gz
	SRR13532700.fastq.gz	Fastqsanger.gz
	SRR13532800.fastq.gz	Fastqsanger.gz
	SRR13532900.fastq.gz	Fastqsanger.gz
	SRR13533000.fastq.gz	Fastqsanger.gz

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Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain [SmartSeq2]

Project description: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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Project description:Molecular characterization of the individual neuron types existing in the primate dorsal root ganglion and the relation to model organisms used for studying somatosensation and pain is critical for understanding the cellular origin of chronic pain and for translational aspects of biomedical research. However, molecular insights into the primate dorsal root ganglion are missing and a systematic comparison of strategies for somatosensation between the mouse and primates is lacking. Here we classify non-human primate sensory neurons based on their transcriptome and identify neuronal types with heritability to chronic pain. We identify nine neuronal types and use machine learning to expose an overall cross-species conserved strategy and shared taxonomy for nociception, although with differences at individual gene level, highlighting the importance of incorporating primate knowledge for the successful translation of discoveries in rodent model organisms. Genomic loci implicated in chronic pain were mapped onto specific primate sensory neuron types to identify the cellular origin of chronic pain. The common-variant genome-wide association results for chronic pain point to the same cells at the same pain sites and concentrate on two different neuronal types between pain disorders, suggesting that causative cell types and molecular mechanisms are different between different pain conditions.

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