Conserved dorsal horn neuron subtype-specific enhancers are implicated in the genetic risk of chronic pain [Mouse Xenium]
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PROVIDER: PRJNA1067992 | ENA |
REPOSITORIES: ENA
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Project description:The dorsal horn of the spinal cord transforms incoming somatosensory information and transmits it supraspinally to generate sensory perception, including pain and itch. Recent research using mouse Cre-driver lines has implicated specific populations of dorsal horn neurons in the transmission of different types of pain. In parallel, human genome-wide association studies (GWAS) have identified dozens of loci confidently associated with the genetic predisposition to chronic pain. The ability to connect controlled experiments in rodent models with human genetic studies could provide a platform for translational research, but the cell type heterogeneity of the dorsal horn and the complex genetic architecture of chronic pain have created challenges in bridging that gap. Here, we apply a variety of single cell genomic technologies and a comparative genomic analysis to identify conserved dorsal horn neuron subtypes whose open chromatin regions show enrichment for genetic variants associated with human chronic pain phenotypes. To achieve this, we first use single nucleus RNA-Seq and fluorescence in situ hybridization in Rhesus macaque to create a more detailed map of primate dorsal horn neuron subtypes. These were integrated with publicly available human and mouse single nucleus RNA-Seq datasets to create a multi-modal cross species atlas. Then, for the mouse dorsal horn, we combined single nucleus RNA-Seq, spatial transcriptomics, and single nucleus ATAC-Seq to infer spatial and epigenomic profiles of conserved dorsal horn neuron subtypes. Finally, we compared our conserved cell-type open chromatin resource to chronic pain GWAS and found that open chromatin regions of specific dorsal horn neuron subtypes showed enrichment for a variety of human chronic pain phenotypes. Our results provide a foundation to further explore how conserved dorsal horn neuron subtypes influence the transmission of pain signals.
2024-08-01 | GSE253951 | GEO
Project description:The dorsal horn of the spinal cord transforms incoming somatosensory information and transmits it supraspinally to generate sensory perception, including pain and itch. Recent research using mouse Cre-driver lines has implicated specific populations of dorsal horn neurons in the transmission of different types of pain. In parallel, human genome-wide association studies (GWAS) have identified dozens of loci confidently associated with the genetic predisposition to chronic pain. The ability to connect controlled experiments in rodent models with human genetic studies could provide a platform for translational research, but the cell type heterogeneity of the dorsal horn and the complex genetic architecture of chronic pain have created challenges in bridging that gap. Here, we apply a variety of single cell genomic technologies and a comparative genomic analysis to identify conserved dorsal horn neuron subtypes whose open chromatin regions show enrichment for genetic variants associated with human chronic pain phenotypes. To achieve this, we first use single nucleus RNA-Seq and fluorescence in situ hybridization in Rhesus macaque to create a more detailed map of primate dorsal horn neuron subtypes. These were integrated with publicly available human and mouse single nucleus RNA-Seq datasets to create a multi-modal cross species atlas. Then, for the mouse dorsal horn, we combined single nucleus RNA-Seq, spatial transcriptomics, and single nucleus ATAC-Seq to infer spatial and epigenomic profiles of conserved dorsal horn neuron subtypes. Finally, we compared our conserved cell-type open chromatin resource to chronic pain GWAS and found that open chromatin regions of specific dorsal horn neuron subtypes showed enrichment for a variety of human chronic pain phenotypes. Our results provide a foundation to further explore how conserved dorsal horn neuron subtypes influence the transmission of pain signals.
2024-08-01 | GSE253953 | GEO
Project description:The dorsal horn of the spinal cord transforms incoming somatosensory information and transmits it supraspinally to generate sensory perception, including pain and itch. Recent research using mouse Cre-driver lines has implicated specific populations of dorsal horn neurons in the transmission of different types of pain. In parallel, human genome-wide association studies (GWAS) have identified dozens of loci confidently associated with the genetic predisposition to chronic pain. The ability to connect controlled experiments in rodent models with human genetic studies could provide a platform for translational research, but the cell type heterogeneity of the dorsal horn and the complex genetic architecture of chronic pain have created challenges in bridging that gap. Here, we apply a variety of single cell genomic technologies and a comparative genomic analysis to identify conserved dorsal horn neuron subtypes whose open chromatin regions show enrichment for genetic variants associated with human chronic pain phenotypes. To achieve this, we first use single nucleus RNA-Seq and fluorescence in situ hybridization in Rhesus macaque to create a more detailed map of primate dorsal horn neuron subtypes. These were integrated with publicly available human and mouse single nucleus RNA-Seq datasets to create a multi-modal cross species atlas. Then, for the mouse dorsal horn, we combined single nucleus RNA-Seq, spatial transcriptomics, and single nucleus ATAC-Seq to infer spatial and epigenomic profiles of conserved dorsal horn neuron subtypes. Finally, we compared our conserved cell-type open chromatin resource to chronic pain GWAS and found that open chromatin regions of specific dorsal horn neuron subtypes showed enrichment for a variety of human chronic pain phenotypes. Our results provide a foundation to further explore how conserved dorsal horn neuron subtypes influence the transmission of pain signals.
2024-08-01 | GSE253952 | GEO
Project description:Ontogeny of the spinal cord dorsal horn [Xenium]
| PRJNA1233804 | ENA
Project description:An exquisite example of form serving function is the dorsal horn of the spinal cord, the gateway to the central nervous system for sensory information from the body. Each sensory input to the dorsal horn targets a specific address within its laminated arrangement of diverse neuronal populations. However, it is not known how this organization emerges during development from an apparently homogenous pool of neural progenitors. Here, we found that both the excitatory and inhibitory cell families of the mouse dorsal horn were born in successive waves as temporal cohorts. The excitatory families then settled into a chronotopic map that transformed their birth order into the dorsal laminae. Diversification of families into refined neuron types was mediated by a dorsal-ventral progenitor gradient of Zic transcription factors. This work uncovered fundamental temporal and spatial factors that establish the cell types and structure of the spinal cord dorsal horn.
2025-08-22 | GSE291460 | GEO
Project description:We generated single cell RNA-seq data to measure the transctiptional profiles of cervicothoracic human pluripotent stem cell-derived dorsal horn spheroids cultured together with human DRG spheroids in an in-vitro model of the dorsal root ganglion-spinal horn dorsal horn pain circuit. hPSC derived dorsal horn interneurons were generated using our previously established protocol and aggregated into spheroids. These spheroids were cultured in a microphysiological device for 5 weeks together with human DRG spheroids created using hiPSC derived nociceptors purchased from Anatomic Inc. In toal we recovered the transcriptomes of 28,445 cells. Analysis verified the presence of the dI4/dI5 cells of the superficial dorsal horn which are implicated in the modeled pain circuit. These cells also expressed a high level of late-born neuronal markers NFIB and Neurod2.
2025-08-01 | GSE303698 | GEO
Project description:To evaluate ac4C acetylation in the spinal dorsal horn of rats with bone cancer pain.
2023-05-23 | GSE225571 | GEO
Project description:Conserved dorsal horn neuron subtype-specific enhancers are implicated in the genetic risk of chronic pain.
| PRJNA1067985 | ENA
Project description:As rats do not develop neuropathic pain like hypersensitivity as neonates post nerve injury but do as adults we have used these arrays to help define the processes involved in this process. Rat spinal cord (ipsilateral dorsal horn) was assayed 7 days post SNI injury to the sciatic nerve relative to sham injury. Two age groups of animals were tested Neonates (P10) and Adult (8-12wks). Experiment Overall Design: Six biologically indepenedent arrays were hybridized per assay point. Dorsal horn total RNA was prepared using standard Affymetrix protocols. Affymetrix Rat Expression 230A array used.
2009-11-10 | E-GEOD-18803 | biostudies-arrayexpress
Project description:Oxaliplatin-induced neuropathic pain is a common dose-limiting side effect of cancer treatment but the underlying mechanisms are largely unknown. The neuropathic pain model was established by oxaliplatin intraperitoneal administration for five consecutive days. In the present study, we performed whole genome expression microarray analysis by using spinal dorsal horn from oxaliplatin-treated and vehicle-treated rats on day 10.
2020-03-11 | GSE146739 | GEO