Spatial Transcriptomics of Dorsal Root Ganglia Identifies Molecular Signatures of Human Nociceptors

Authors

Diana Tavares-Ferreira
Stephanie Shiers
Pradipta R Ray
Andi Wangzhou
Vivekanand Jeevakumar
Ishwarya Sankaranarayanan
Anna M Cervantes
Jeffrey C Reese
Alexander Chamessian
Bryan A Copits
Patrick M Dougherty
Robert W Gereau
Michael D Burton
Gregory Dussor
Theodore J Price

Publication Date

2-16-2022

Journal

Science Translational Medicine

Abstract

Nociceptors are specialized sensory neurons that detect damaging or potentially damaging stimuli and are found in the dorsal root ganglia (DRG) and trigeminal ganglia. These neurons are critical for the generation of neuronal signals that ultimately create the perception of pain. Nociceptors are also primary targets for treating acute and chronic pain. Single-cell transcriptomics on mouse nociceptors has transformed our understanding of pain mechanisms. We sought to generate equivalent information for human nociceptors with the goal of identifying transcriptomic signatures of nociceptors, identifying species differences and potential drug targets. We used spatial transcriptomics to molecularly characterize transcriptomes of single DRG neurons from eight organ donors. We identified 12 clusters of human sensory neurons, 5 of which are C nociceptors, as well as 1 C low-threshold mechanoreceptors (LTMRs), 1 Aβ nociceptor, 2 Aδ, 2 Aβ, and 1 proprioceptor subtypes. By focusing on expression profiles for ion channels, G protein-coupled receptors (GPCRs), and other pharmacological targets, we provided a rich map of potential drug targets in the human DRG with direct comparison to mouse sensory neuron transcriptomes. We also compared human DRG neuronal subtypes to nonhuman primates showing conserved patterns of gene expression among many cell types but divergence among specific nociceptor subsets. Last, we identified sex differences in human DRG subpopulation transcriptomes, including a marked increase in calcitonin-related polypeptide alpha (

Keywords

Animals, Chronic Pain, Female, Ganglia, Spinal, Humans, Male, Mice, Nociceptors, Sensory Receptor Cells, Transcriptome

DOI

10.1126/scitranslmed.abj8186

PMID

35171654

PMCID

PMC9272153

PubMedCentral® Posted Date

2-16-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes