Cross-species transcriptomic atlas of dorsal root ganglia reveals species-specific programs for sensory function

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 23, 2023

Sensory neurons of the dorsal root ganglion (DRG) are critical for maintaining tissue homeostasis by sensing and initiating responses to stimuli. While most preclinical studies DRGs conducted in rodents, much less is known about mechanisms sensory perception primates. We generated a transcriptome atlas mouse, guinea pig, cynomolgus monkey, human implementing common laboratory workflow multiple data-integration approaches generate high-resolution cross-species mappings neuron subtypes. Using our atlas, we identified conserved core modules highlighting subtype-specific biological processes related inflammatory response. also divergent expression key genes involved DRG function, suggesting species-specific adaptations specifically nociceptors that likely point function nociceptors. Among these, validated TAFA4, member druggable genome, was expressed distinct populations across species, programs therapeutic development.

Language: Английский

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Human and mouse trigeminal ganglia cell atlas implicates multiple cell types in migraine

Neuron, Journal Year: 2022, Volume and Issue: 110(11), P. 1806 - 1821.e8

Published: March 28, 2022

Language: Английский

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PIEZO1 transduces mechanical itch in mice

Nature, Journal Year: 2022, Volume and Issue: 607(7917), P. 104 - 110

Published: June 22, 2022

Itch triggers scratching, a behavioural defence mechanism that aids in the removal of harmful irritants and parasites1. Chemical itch is triggered by many endogenous exogenous cues, such as pro-inflammatory histamine, which released during an allergic reaction1. Mechanical can be light sensations wool fibres or crawling insect2. In contrast to chemical pathways, have been extensively studied, mechanisms underlie transduction mechanical are largely unknown. Here we show mechanically activated ion channel PIEZO1 (ref. 3) selectively expressed itch-specific sensory neurons required for their currents. Loss function peripheral greatly reduces evoked scratching behaviours both acute chronic itch-evoked sensitization. Finally, mice expressing gain-of-function Piezo1 allele4 exhibit enhanced behaviours. Our studies reveal polymodal nature identify role sensation itch.

Language: Английский

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Advances in spatial transcriptomics and related data analysis strategies

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 18, 2023

Spatial transcriptomics technologies developed in recent years can provide various information including tissue heterogeneity, which is fundamental biological and medical research, have been making significant breakthroughs. Single-cell RNA sequencing (scRNA-seq) cannot spatial information, while allow gene expression to be obtained from intact sections the original physiological context at a resolution. Various insights generated into architecture further elucidation of interaction between cells microenvironment. Thus, we gain general understanding histogenesis processes disease pathogenesis, etc. Furthermore, silico methods involving widely distributed R Python packages for data analysis play essential roles deriving indispensable bioinformation eliminating technological limitations. In this review, summarize available transcriptomics, probe several applications, discuss computational strategies raise future perspectives, highlighting developmental potential.

Language: Английский

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S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis

Cell, Journal Year: 2023, Volume and Issue: 186(24), P. 5375 - 5393.e25

Published: Nov. 1, 2023

Language: Английский

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Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease

Acta Neuropathologica Communications, Journal Year: 2022, Volume and Issue: 10(1)

Published: Dec. 21, 2022

Abstract Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer’s disease (AD), but little known about the molecular mechanisms underlying this regional vulnerability. Here we utilize 10 × Visium platform to define spatial transcriptomic profile both AD and control (CT) MTG. We identify unique marker genes for cortical layers white matter, layer-specific differentially expressed (DEGs) human compared CT. Deconvolution of spots showcases significant difference particular cell types among matter. Gene co-expression analyses reveal eight gene modules, four which have significantly altered patterns presence pathology. The hub enriched pathways pathology indicate an important role cell–cell-communications microglia, oligodendrocytes, astrocytes, neurons, may contribute cellular vulnerability AD. Using single-molecule fluorescent situ hybridization, validated cell-type-specific expression three novel DEGs (e.g., KIF5A , PAQR6 SLC1A3 ) eleven previously reported associated with (i.e., amyloid beta plaques intraneuronal neurofibrillary tangles or neuropil threads) at single level. Our results understanding complex architecture neuronal glial response region.

Language: Английский

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A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes

Cell, Journal Year: 2024, Volume and Issue: 187(6), P. 1508 - 1526.e16

Published: March 1, 2024

Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from periphery to CNS has been challenging with existing tools. Here, we develop curate mouse genetic toolkit that allows for interrogating properties functions distinct cutaneous targeting subtypes. These tools have enabled broad morphological analysis, which revealed axon arborization areas branching patterns transcriptionally Moreover, in vivo physiological analysis each subtype threshold range responses mechanical and/or thermal stimuli. findings support model morphologically physiologically sensory tile stimulus space collectively encode wide natural

Language: Английский

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Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 29, 2023

Non-opioid targets are needed for addressing osteoarthritis pain, which is mechanical in nature and associated with daily activities such as walking climbing stairs. Piezo2 has been implicated the development of but mechanisms by this occurs remain poorly understood, including role nociceptors. Here we show that nociceptor-specific conditional knock-out mice were protected from sensitization inflammatory joint pain female mice, male well both knee swelling repeated intra-articular injection nerve growth factor mice. Single cell RNA sequencing mouse lumbar dorsal root ganglia situ hybridization human revealed a subset nociceptors co-express Ntrk1 (the gene encodes receptor TrkA). These results suggest factor-mediated nociceptors, critical osteoarthritic also dependent on Piezo2, targeting may represent therapeutic option control.

Language: Английский

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

Science Advances, Journal Year: 2024, Volume and Issue: 10(25)

Published: June 21, 2024

Sensory neurons in the dorsal root ganglion (DRG) and trigeminal (TG) are specialized to detect transduce diverse environmental stimuli central nervous system. Single-cell RNA sequencing has provided insights into diversity of sensory ganglia cell types rodents, nonhuman primates, humans, but it remains difficult compare across studies species. We thus constructed harmonized atlases DRG TG that describe facilitate comparison 18 neuronal 11 non-neuronal six species 31 datasets. then performed single-cell/nucleus from both human highly regenerative axolotl found atlas also improves type annotation, particularly sparse subtypes. observed transcriptomes neuron subtypes broadly similar vertebrates, expression functionally important neuropeptides channels can vary notably. The resources presented here guide future comparative transcriptomics, simplify cell-type nomenclature differences studies, help prioritize targets for analgesic development.

Language: Английский

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Pathology of pain and its implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 8, 2024

Abstract Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management crucial for individuals suffering from pain. However, current methods assessment treatment fall short clinical needs. Benefiting advances in neuroscience biotechnology, neuronal circuits molecular mechanisms critically involved modulation have been elucidated. These research achievements incited progress identifying new diagnostic therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting stage subsequent contents. The review next delves into underlying disorders, including gene mutation, epigenetic modification, posttranslational inflammasome, signaling pathways microbiota. To better present a comprehensive view research, two prominent issues, sexual dimorphism comorbidities, are discussed detail based on findings. status quo evaluation manipulation summarized. A series improved innovative strategies, such as therapy, monoclonal antibody, brain-computer interface microbial intervention, making strides towards application. We highlight existing limitations future directions enhancing quality preclinical research. Efforts decipher complexities pathology will be instrumental translating scientific discoveries practice, thereby improving bench bedside.

Language: Английский

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