Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia

Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia

21 June 2024 | Shamsuddin A. Bhuiyan, Mengyi Xu, Lite Yang, Evangelia Semizoglou, Parth Bhatia, Katerina I. Pantaleo, Ivan Tochitsky, Aakansha Jain, Burcu Erdogan, Steven Blair, Victor Cat, Juliet M. Mwirigi, Ishwarya Sankaranarayanan, Diana Tavares-Ferreira, Ursula Green, Lisa A. McIlvried, Bryan A. Copits, Zachariah Bertels, John S. Del Rosario, Allie J. Widman, Richard A. Slivicki, Jiwon Yi, Reza Sharif-Naeini, Clifford J. Woolf, Jochen K. Lennerth, Jessica L. White, Theodore J. Price, Robert W. Gereau IV, William Renthal
The study presents harmonized cross-species cell atlases of the dorsal root ganglion (DRG) and trigeminal ganglion (TG), identifying 18 neuronal and 11 non-neuronal cell types across six species and 31 datasets. These atlases improve cell type annotation, particularly for sparse neuronal subtypes, and reveal broad similarities in the transcriptomes of sensory neuron subtypes across vertebrates, with notable variations in functionally important neuropeptides and channels. The resources enable comparative transcriptomics, simplify cell-type nomenclature, and aid in prioritizing targets for future analgesic development. The DRG and TG contain both neuronal and non-neuronal cells, including satellite glia, Schwann cells, immune cells, and fibroblasts, which play roles in ganglion structure and modulating peripheral sensory neuron properties. Sensory neuron subtypes are historically classified by size, myelination, conduction velocity, and gene expression. A-fibers are large-diameter, fast-conducting neurons, while C-fibers are unmyelinated, slow-conducting neurons. A-fibers are specialized for mechanical stimuli, whereas C-fibers detect a broader range of stimuli, including thermal, mechanical, and chemical. The study used single-cell/nucleus RNA sequencing (sc/snRNA-seq) to construct harmonized atlases, enabling the harmonization of cell-type nomenclatures, direct comparisons between studies and species, improved transcriptomic coverage of lowly expressed genes, and identification of rare cell populations. The harmonized DRG neuronal reference atlas contains 18 neuronal subtypes, while the TG neuronal reference atlas contains 15. These include A-fiber and C-fiber subtypes with known functions, as well as putative C-fiber subtypes without known functions. The non-neuronal atlases identified 11 non-neuronal cell types, including glial, endothelial, fibroblast, and immune cells. These include satellite glia, myelinating and non-myelinating Schwann cells, and immune cells such as neutrophils, monocytes, B cells, T cells, dendritic cells, and macrophages. The study also mapped ligand-receptor (LR) interactions across immune and neuronal cell types, revealing interactions that may contribute to immune cell memory and residency in the DRG and TG. The harmonized atlas improved transcriptomic coverage compared to individual studies, particularly for rare cell populations. It also improved the annotation of human DRG snRNA-seq data, enabling the identification of more neuronal subtypes and improving the granularity of annotations. The atlas revealed similarities and differences in human and mouse sensory ganglia, with conserved gene expression patterns and notable species differences in functionally important genes. The study also compared cell-type-specific transcriptomes across mammals, vertebrates, and invertebrates, finding broad similarities in gene expression across speciesThe study presents harmonized cross-species cell atlases of the dorsal root ganglion (DRG) and trigeminal ganglion (TG), identifying 18 neuronal and 11 non-neuronal cell types across six species and 31 datasets. These atlases improve cell type annotation, particularly for sparse neuronal subtypes, and reveal broad similarities in the transcriptomes of sensory neuron subtypes across vertebrates, with notable variations in functionally important neuropeptides and channels. The resources enable comparative transcriptomics, simplify cell-type nomenclature, and aid in prioritizing targets for future analgesic development. The DRG and TG contain both neuronal and non-neuronal cells, including satellite glia, Schwann cells, immune cells, and fibroblasts, which play roles in ganglion structure and modulating peripheral sensory neuron properties. Sensory neuron subtypes are historically classified by size, myelination, conduction velocity, and gene expression. A-fibers are large-diameter, fast-conducting neurons, while C-fibers are unmyelinated, slow-conducting neurons. A-fibers are specialized for mechanical stimuli, whereas C-fibers detect a broader range of stimuli, including thermal, mechanical, and chemical. The study used single-cell/nucleus RNA sequencing (sc/snRNA-seq) to construct harmonized atlases, enabling the harmonization of cell-type nomenclatures, direct comparisons between studies and species, improved transcriptomic coverage of lowly expressed genes, and identification of rare cell populations. The harmonized DRG neuronal reference atlas contains 18 neuronal subtypes, while the TG neuronal reference atlas contains 15. These include A-fiber and C-fiber subtypes with known functions, as well as putative C-fiber subtypes without known functions. The non-neuronal atlases identified 11 non-neuronal cell types, including glial, endothelial, fibroblast, and immune cells. These include satellite glia, myelinating and non-myelinating Schwann cells, and immune cells such as neutrophils, monocytes, B cells, T cells, dendritic cells, and macrophages. The study also mapped ligand-receptor (LR) interactions across immune and neuronal cell types, revealing interactions that may contribute to immune cell memory and residency in the DRG and TG. The harmonized atlas improved transcriptomic coverage compared to individual studies, particularly for rare cell populations. It also improved the annotation of human DRG snRNA-seq data, enabling the identification of more neuronal subtypes and improving the granularity of annotations. The atlas revealed similarities and differences in human and mouse sensory ganglia, with conserved gene expression patterns and notable species differences in functionally important genes. The study also compared cell-type-specific transcriptomes across mammals, vertebrates, and invertebrates, finding broad similarities in gene expression across species
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