1. Spatial, transcriptomic, and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition.
- Author
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Arokiaraj CM, Leone MJ, Kleyman M, Chamessian A, Noh MC, Phan BN, Lopes BC, Corrigan KA, Cherupally VK, Yeramosu D, Franusich ME, Podder R, Lele S, Shiers S, Kang B, Kennedy MM, Chen V, Chen Z, Mathys H, Dum RP, Lewis DA, Qadri Y, Price TJ, Pfenning AR, and Seal RP
- Abstract
Key mechanisms underlying chronic pain occur within the dorsal horn. Genome-wide association studies (GWASs) have identified genetic variants predisposed to chronic pain. However, most of these variants lie within regulatory non-coding regions that have not been linked to spinal cord biology. Here, we take a multi-species approach to determine whether chronic pain variants impact the regulatory genomics of dorsal horn neurons. First, we generate a large rhesus macaque single-nucleus RNA sequencing (snRNA-seq) atlas and integrate it with available human and mouse datasets to produce a single unified, species-conserved atlas of neuron subtypes. Cellular-resolution spatial transcriptomics in mouse shows the precise laminar location of these neuron subtypes, consistent with our analysis of neuron-subtype-selective markers in macaque. Using this cross-species framework, we generate a mouse single-nucleus open chromatin atlas of regulatory elements that shows strong and selective relationships between the neuron-subtype-specific chromatin regions and variants from major chronic pain GWASs., Competing Interests: Declaration of interests A.R.P. is the founder of Snail Biosciences, Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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