A Reference Atlas of the Human Dorsal Root Ganglion

作者：Shamsuddin A. Bhuiyan, Saad S. Nagi, Ishwarya Sankaranarayanan, Evangelia Semizoglou, Dmitry Usoskin, Lite Yang, Huasheng Yu, Asta Arendt-Tranholm, Zachariah Bertels, Parth Bhatia, Otmane Bouchatta, Kevin Boyer, Anna Cervantes, Joshua I. Chalif, Himanshu Chintalapudi, Anthony Cicalo, Bryan A. Copits, Caitlin Cronin, Michele Curatolo, Xianjun Dong, Patrick M. Dougherty, Adam J. Dourson, Geoffrey Funk, Katherin Gabriel, Dustin S. Griesemer, Hong Guo, Prashant Gupta, Christoph Hofstetter, Peter Horton, Amanda Hsieh, Nikhil Nageshwar Inturi, Aakanksha Jain, Selwyn S. Jayakar, Benjamin Johnston, Rebecca Kim, Doris Krauter, Jussi Kupari, John Lemen, Joseph B. Lesnak, Weiqiang Liu, I. López, Yi Lu, Hannah J. MacMillan, Khadijah Mazhar, Pauline Meriau, Jeffrey R. Moffitt, Marisol Mancilla Moreno, Juliet M. Mwirigi, Huma Naz, Jayden O’Brein, Maria Payne, John Smith Del Rosario, Sarah F. Rosen, Stephanie Shiers, Ebenezer Simpson, Richard A. Slivicki, James R. Stone, Diana Tavares‐Ferreira, Megan L. Uhelski, Clifford J. Woolf, Qingru Xu, Jiwon Yi, Muhammad Saad Yousuf, Difei Zhu, Valeria Cavalli, Guoyan Zhao, Håkan Olausson, Patrik Ernfors, Robert W. Gereau, Wenqin Luo, Theodore J. Price, William Renthal, NIH PRECISION Human Pain Network · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.1101/2025.11.05.686654 · 被引用次数：17 · 研究领域：Pain Mechanisms and Treatments、Nerve injury and regeneration、Fibromyalgia and Chronic Fatigue Syndrome Research

Somatosensory perception largely emerges from diverse peripheral sensory neurons whose cell bodies reside in dorsal root ganglia (DRG). Damage or dysfunction of DRG neurons is a major cause of chronic pain and sensory loss. In mice, deep single-cell transcriptomic profiling and genetically defined models have offered important clues into DRG function, but in humans, the cellular and molecular landscape of DRG neurons remains less understood. Here, we constructed a reference cell atlas of the human DRG by profiling transcriptomes of cells and nuclei from 126 donors sampled across cervical, thoracic, and lumbar DRGs. This atlas resolves 22 neuronal subtypes, including known and previously unrecognized subtypes linked to nociception, mechanosensation, thermosensation, and proprioception, as well as 10 types of non-neuronal cells. Cross-species integration, spatial transcriptomics, and microneurography enabled cell-type-specific comparisons of soma size and conduction velocity between species. Human DRG somata are larger across all cell types than their mouse counterparts, and the conduction velocities of human hair follicle innervating A-fibers are faster than in mice, suggesting a functional shift in rapid mechanical detection in humans. This integrated human DRG reference cell atlas provides a resource for exploring new molecular and physiological features of human DRG, which could help identify new strategies for treating chronic pain and other diseases of the peripheral nerv...