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.
Project description:We have used large-scale single-cell RNA sequencing (RNA-seq) to classify sensory neurons in the mouse dorsal horn, with the purpose of identifying neuronal subclasses, in particular making a systematic and comprehensive molecular classification of spinal cord sensory neurons, providing the neuronal basis for somatic sensation.
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.
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.
Project description:Here we performed a ChIP-seq experiment for Tlx3 trancription factor on a sample of mouse embryonic dorsal spinal cord. The result is the generation of the genome-wide maps for Tlx3 binding to chromatin in dILB neurones of the developing dorsal horn.
Project description:This SuperSeries is composed of the following subset Series: GSE21258: Transcript Profiling of Spinal Dorsal Horn in Response to Electroacupuncture on Rats at 1h GSE21733: Transcript Profiling of Spinal Dorsal Horn in Response to Electroacupuncture on Rats at 24h Refer to individual Series
Project description:Endometrial remodeling is required for implantation in all mammalian species. To identify the factors that promote cell proliferation at the implantation site were explored in bovine endometrium and extra-embryonic membrane during the peri-implantation period. Microarray analysis showed that the expression levels of various trophoblast specific genes were higher in the extra-embryonic membrane at gravid horn than in the extra-embryonic membrane at non-gravid horn namely, CSH1, PRPs, PAGs, AIF, Muc-1, etc. Furthermore, EGFR, INHBA and INHBB expression were higher in endometrium of gravid horn.
Project description:Endometrial remodeling is required for implantation in all mammalian species. To identify the factors that promote cell proliferation at the implantation site were explored in bovine endometrium and extra-embryonic membrane during the peri-implantation period. Microarray analysis showed that the expression levels of various trophoblast specific genes were higher in the extra-embryonic membrane at gravid horn than in the extra-embryonic membrane at non-gravid horn namely, CSH1, PRPs, PAGs, AIF, Muc-1, etc. Furthermore, EGFR, INHBA and INHBB expression were higher in endometrium of gravid horn. Gene expression profiles were analyzed in the gravid and non-gravid extra-embryonic membrane and endometrium at around Day 30 of gestation
Project description:In the present study, a quantitative proteomic approach was used to analyse and compare the proteome in horns from endangered species (rhinoceros, Saiga antelope, and Tibetan antelope) and common species (yak, water buffalo, and goat) based on the isobaric tag for relative and absolute quantification (iTRAQ) techniques. In total, 591 proteins were identified, and 321 were quantified and categorised based on molecular function, cellular component, and biological process. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) results based on differences in the amount of protein identified three major clusters, and proteins including transglutaminase, desmocollin, and elongation factors were selected as trait components from proteomic patterns of horn samples from different species. Quantitative proteomic analysis-based strategies can therefore provide further evidence for sustainable alternatives to replace animal horn from threatened species.