The emergence of transcriptional identity in somatosensory neurons
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ABSTRACT:
PROVIDER: PRJNA578356 | ENA |
REPOSITORIES: ENA
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Project description:Primary somatosensory neurons are diverse neurons that report salient features of our internal and external environments. How specialized gene expression programs emerge during development to endow each somatosensory neuron subtype with unique properties is unclear. To analyze the developmental progression of transcriptional maturation of each principal somatosensory neuron subtype, we generated a transcriptomic atlas of cells traversing the somatosensory lineage. We find that somatosensory neurogenesis leads to neurons in a transcriptionally unspecialized state, characterized by trace expression of subtype-specific genes yet co-expression of transcription factors (TFs) that become restricted to select subtypes as development proceeds. Single cell transcriptomic analysis using sensory neurons from mutant mice lacking representative broad-to-restricted TFs revealed that they are essential for establishing subtype specific gene programs in subtypes where their expression is maintained, while leaving other subtypes unaffected. We also identify a role for neuronal targets by demonstrating that nerve growth factor influences subtype-restricted patterns of TFs. Our findings support a model in which extrinsic cues orchestrate somatosensory neuron diversification by influencing the expression pattern of TFs that promote transcriptional specialization of somatosensory neuron subtypes.
2019-10-19 | GSE139088 | GEO
Project description: Not available
| S-EPMC7307422 | biostudies-literature
Project description:In mice, spared nerve injury replicates symptoms of human neuropathic pain and induces upregulation of many genes in somatosensory neurons. Here we used single cell transcriptomics to probe the effects of partial infraorbital transection of the trigeminal nerve at the cellular level. Uninjured neurons were unaffected by transection of major nerve branches, segregating into many different classes. In marked contrast, axotomy rapidly transformed damaged neurons into just two new and closely-related classes where almost all original identity was lost. Remarkably, sensory neurons also adopted this transcriptomic state following various minor peripheral injuries. By genetically marking injured neurons, we showed that the injuryinduced transformation was reversible, with damaged cells slowly reacquiring normal gene expression profiles. Thus, our data expose transcriptomic plasticity, previously thought of as a driver of chronic pain, as a programed response to many types of injury and a potential mechanism for regulating sensation during wound healing.
2019-10-04 | GSE131272 | GEO
Project description:Single-cell RNA sequencing has generated the first catalogs of transcriptionally defined neuronal subtypes of the brain. However, the cellular processes that contribute to neuronal subtype specification and transcriptional heterogeneity remain unclear. By comparing the gene expression profiles of a subset of single layer 6 corticothalamic neurons in somatosensory cortex, we show that transcriptional subtypes primarily reflect axonal projection pattern, laminar position within the cortex, and neuronal activity state. Pseudotemporal ordering of 1023 cellular responses to sensory manipulation demonstrates that changes in expression of activity-induced genes both reinforced cell-type identity and contributed to increased transcriptional heterogeneity within each cell type. This is due to cell-type biased choices of transcriptional states following manipulation of neuronal activity. These results reveal that axonal projection pattern, laminar position, and activity state define significant axes of variation that contribute both to the transcriptional identity of individual neurons and to the transcriptional heterogeneity within each neuronal subtype.
2017-12-31 | GSE107632 | GEO
Project description:The goal of this study was to analyze global gene expression in specific populations of somatosensory neurons in the periphery, including major, non-overlapping populations that include nociceptors, pruriceptors, and prorioceptors. The mammalian somatosensory nervous system encodes the perception of specific environmental stimuli. The dorsal root ganglion (DRG) contains distinct somatosensory neuron subtypes that innervate diverse peripheral tissues, mediating the detection of thermal, mechanical, proprioceptive, pruriceptive, and nociceptive stimuli. We purified discrete subtypes of mouse DRG somatosensory neurons by flow cytometry using fluorescently labeled mouse lines (SNS-Cre/TdTomato, Parv-Cre/TdTomato) in combination with Isolectin B4-FITC surface staining (IB4). This allowed identification of transcriptional differences between these major populations, revealing enrichment of voltage-gated ion channels, TRP channels, G-protein coupled receptors, transcription factors, and other functionally important classes of genes within specific somatosensory neuron subsets. SNS-Cre mice were bred with Rosa26-TdTomato mice to generate SNS-Cre/TdTomato reporter mice. Parv-Cre mice were bred with Rosa26-TdTomato mice to generate Parv-Cre/TdTomato mice. Isolectin B4-FITC was used to stain the surface of SNS-Cre/TdTomato reporter mice. We used these strategies of fluorescent labeling to purify distinct murine sensory neuron subsets from the dorsal root ganglia (DRG) by fluorescence activated cell sorting (FACS). Neurons were sorted directly in Qiazol for total RNA extraction and microarray analysis. Whole DRG tissue was also included for transcriptome analysis to compare with purified neuronal populations.
2014-12-23 | E-GEOD-55114 | biostudies-arrayexpress
Project description:The goal of this study was to analyze global gene expression in specific populations of somatosensory neurons in the periphery, including major, non-overlapping populations that include nociceptors, pruriceptors, and prorioceptors. The mammalian somatosensory nervous system encodes the perception of specific environmental stimuli. The dorsal root ganglion (DRG) contains distinct somatosensory neuron subtypes that innervate diverse peripheral tissues, mediating the detection of thermal, mechanical, proprioceptive, pruriceptive, and nociceptive stimuli. We purified discrete subtypes of mouse DRG somatosensory neurons by flow cytometry using fluorescently labeled mouse lines (SNS-Cre/TdTomato, Parv-Cre/TdTomato) in combination with Isolectin B4-FITC surface staining (IB4). This allowed identification of transcriptional differences between these major populations, revealing enrichment of voltage-gated ion channels, TRP channels, G-protein coupled receptors, transcription factors, and other functionally important classes of genes within specific somatosensory neuron subsets.
2014-12-23 | GSE55114 | GEO
Project description:Transcriptional adaptation of olfactory sensory neurons to GPCR identity and activity
| PRJNA767851 | ENA
Project description:Stereotyped transcriptomic transformation of somatosensory neurons in response to injury
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Project description:Transcriptional adaptation of olfactory sensory neurons to GPCR identity and activity [scRNAseq_MOE_rest]
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Project description:Transcriptional adaptation of olfactory sensory neurons to GPCR identity and activity [M71]
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