Stereotyped transcriptomic transformation of somatosensory neurons in response to injury
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ABSTRACT:
PROVIDER: PRJNA543101 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9060650_1.fastq.gz | Fastqsanger.gz | |||
| SRR9060650_2.fastq.gz | Fastqsanger.gz | |||
| SRR9060660_1.fastq.gz | Fastqsanger.gz | |||
| SRR9060660_2.fastq.gz | Fastqsanger.gz | |||
| SRR9060670_1.fastq.gz | Fastqsanger.gz |
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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: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 injury-induced 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.
| S-EPMC6783272 | biostudies-literature
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:The emergence of transcriptional identity in somatosensory neurons
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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:Microarray analysis of control and Lhx2 cKO somatosensory cortices to determine differentially expressed genes at P7 resulting from the loss of Lhx2 in post-mitotic neurons.
2016-12-15 | GSE92372 | 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.
2014-12-23 | GSE55114 | GEO
Project description:Deep sequencing of somatosensory neurons reveals molecular determinants of intrinsic physiological properties
| PRJNA543018 | ENA
Project description:Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron typing with the sensory phenotypes. Here we classify somatosensory neurons of the mouse dorsal root ganglion (DRG) by high-coverage single-cell RNA-sequencing (10 950 ± 1 218 genes per neuron) and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli are recorded using an in vivo whole-cell patch clamp technique and classified by neuron-type genetic markers. Small diameter DRG neurons are classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptors (MHNs). Each of the MHN types is further categorized into two subtypes. Large DRG neurons are categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors (MNs) expressing BAI1-associated protein 2-like 1 (Baiap2l1). Mechanoreceptors expressing trafficking protein particle complex 3-like and Baiap2l1-marked MNs are subdivided into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases. RNA-seq of mRNA levels in 197 individual DRG neurons We performed RNA-seq on total 203 individual DRG neurons. Six of them were not qualified and thus, were excluded for further analysis. To evaluate the quality of RNA-seq, we randomly devided No.72 neurons into two parts and performed RNA-seq seperately. Thus, we had 204 individual samples from 203 individual DRG and 198 individual qualified samples from 197 individual DRG. To evaluate the homogeneity of RNA-seq data from different mice at the same age just as used, we performed RNA-seq on 5 single DRG from different mice. Here, these data from DRG were also considered as experimental control. The 'DRG_neurons_RNA_Seq.txt' contains processed data for 204 samples and 'DRG_RNA_Seq.txt' for 5 samples.
2015-12-10 | E-GEOD-63576 | biostudies-arrayexpress
Project description:Sensory neuron mechanically-activated slowly adapting currents have been linked to noxious mechanosensation. We identified a Conotoxin, Noxious Mechanosensation Blocker -1, that blocks such currents selectively. Using an active biotinylated form of the toxin we identified 67 binding proteins in sensory neurons and sensory neuron-derived cell lines using mass spectrometry. Annexin A6 was the most frequently identified binding protein. Annexin A6 knockout mice showed an enhanced sensitivity to mechanical stimuli. Rapidly adapting currents were enhanced and slowly adapting channels diminished. The percentage of neurons expressing slowly adapting currents fell and non-responsive neurons increased. Conversely, overexpression of annexin A6 in DRG neurons inhibited rapidly adapting currents without effects on slowly adapting currents. Co-expression of annexin A6 with Piezo 2 led to an inhibition of Piezo-mediated rapidly adapting currents. AAV-mediated gene delivery of annexin A6 to sensory neurons in a mouse model of osteoarthritis attenuated mechanical pain. These data demonstrate a role for annexin A6 in somatosensory mechanotransduction.
2018-04-17 | PXD005718 | Pride