Cellular and Molecular Organization of the Rhesus Macaque Dorsal Horn with a Comparison to Mouse

Arokiaraj, C.; Kleyman, M.; Chamessian, A.; Shiers, S.; Kang, B.; Kennedy, M.; Chen, Y.; Dum, R.; Patterson, R.; Lewis, D.; Qadri, Y.; Levine, A.; Price, T.; Pfenning, A.; Seal, R.

doi:10.1101/2022.04.01.486135

bioRxiv · 10.1101/2022.04.01.486135

Cellular and Molecular Organization of the Rhesus Macaque Dorsal Horn with a Comparison to Mouse

Arokiaraj, C.·Kleyman, M.·Chamessian, A.·Shiers, S.·Kang, B.·Kennedy, M.·Chen, Y.·Dum, R.·Patterson, R.·Lewis, D.·Qadri, Y.·Levine, A.·Price, T.·Pfenning, A.·Seal, R.

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Abstract

Key mechanisms underlying chronic pain occur within the neural circuitry of the dorsal horn. Recent genome-wide association studies (GWAS) have identified genetic variants associated with the predisposition to chronic pain. However, most of these variants lie in regulatory non-coding regions that have so far not been linked to spinal cord function. Here, we take a multi-species approach to determine whether chronic pain variants impact regulatory elements of dorsal horn neurons. We first built a more comprehensive single cell atlas; filling gaps by generating a high-quality Rhesus macaque atlas and integrating it with human and mouse. With cellular-resolution spatial transcriptomics, we mapped the laminar distributions of the resulting species-conserved neuron subtypes, uncovering an unexpected organization. Lastly, we generated a mouse single-nucleus open chromatin atlas to partition the heritability of chronic pain traits. From this, we identified strong, selective associations between specific, conserved neuron subtypes and major forms of chronic pain.

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Arokiaraj, C., Kleyman, M., Chamessian, A., Shiers, S., Kang, B., Kennedy, M., Chen, Y., Dum, R., Patterson, R., Lewis, D., Qadri, Y., Levine, A., Price, T., Pfenning, A., Seal, R.. 2022-04-05. Cellular and Molecular Organization of the Rhesus Macaque Dorsal Horn with a Comparison to Mouse. https://doi.org/10.1101/2022.04.01.486135

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