Biology subjects

Copits, B.

Publications and source records attributed to Copits, B..

3 recordsLinked to original sources

bioRxiv2025

A Reference Atlas of the Human Dorsal Root Ganglion

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 nervous system.

neuroscience↗

bioRxiv2021

Cellular, Circuit and Transcriptional Framework for Modulation of Itch in the Central Amygdala

Itch is an unpleasant sensation that elicits robust scratching and active avoidance. However, the identity of the cells and neural circuits that organize this information remains elusive. Here we show the necessity and sufficiency of itch-activated neurons in the central amygdala (CeA) for both itch sensation and active avoidance. Further, we show that itch-activated CeA neurons play important roles in itch-related comorbidities, including anxiety-like behaviors, but not in some aversive and appetitive behaviors previously ascribed to CeA neurons. RNA-sequencing of itch-activated CeA neurons identified several differentially expressed genes as well as potential key signaling pathways in regulating pruritis. Finally, viral tracing experiments demonstrate that these neurons send a critical projection to the periaqueductal gray to mediate modulation of itch. These findings reveal a cellular and circuit signature of CeA neurons orchestrating behavioral and affective responses to pruritus in mice.

neuroscience↗

bioRxiv2021

Spatial transcriptomics reveals unique molecular fingerprints of human nociceptors

Nociceptors are specialized sensory neurons that detect damaging or potentially damaging stimuli and are found in the dorsal root (DRG) and trigeminal ganglia. These neurons are critical for the generation of neuronal signals that ultimately create the perception of pain. These neurons are also primary targets for acute and chronic pain therapeutics. 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 elucidating new drug targets. We used spatial transcriptomics to molecularly characterize transcriptomes of single dorsal root ganglion (DRG) neurons from 8 organ donors. We identified 12 clusters of human sensory neurons, 5 of which are C nociceptors; as well as 1 A{beta} nociceptor, 2 A{delta}, 2 A{beta} and 1 proprioceptor subtypes. By focusing on expression profiles for ion channels, G-protein coupled receptors (GPCRs) and other pharmacological targets, we provide a rich map of drug targets in the human DRG with direct comparison to mouse sensory neuron transcriptomes. We also compare human DRG neuronal subtypes to non-human primates showing conserved patterns of gene expression among many cell types, but divergence among specific nociceptor subsets. Finally, we identify sex differences in human DRG subpopulation transcriptomes, including a marked increase in CALCA expression in female pruritogen receptor enriched nociceptors. Our data open the door to development of drug discovery programs for new pain targets and unparalleled molecular characterization of clinical sensory disorders. One Sentence SummaryWe used spatial transcriptomics to molecularly characterize human sensory neurons, comparing them to mouse and non-human primate finding similarities but also divergence, in particular among drug targets.

neuroscience↗