ScRNAseq analysis of mouse WT and Fmr1KO dorsal root ganglions
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE176449 | GEO | 2021/11/27
REPOSITORIES: GEO
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Project description:Peripheral sensory neurons located in dorsal root ganglia relay sensory information from the peripheral tissue to the brain. Satellite glial cells (SGC) are unique glial cells that form an envelope completely surrounding each sensory neuron soma. This organization allows for close bi-directional communication between the neuron and it surrounding glial coat. Morphological and molecular changes in SGC have been observed in pathological conditions such as inflammation, chemotherapy-induced neuropathy, viral infection and nerve injuries. SGC play critical roles in neuronal excitability and nociception, as well as contribute to promote axon regeneration. Whether findings made in rodent model systems are relevant to human physiology has not been investigated. Here we present a detailed characterization of SGC across species. We characterized the transcriptional profile of SGC in mouse, rat and human at the single cell level. Our findings suggest that key features of SGC in rodent models are conserved in human. These results support the notion that SGC in the sensory system are largely conserved between species. Our study provides the potential to leverage on rodent and human SGC properties and unravel novel mechanisms and potential targets for treating nerve injuries.
2022-04-14 | GSE169301 | GEO
Project description:Peripheral sensory neurons with cell body in dorsal root ganglia (DRG) switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Studies of nerve injury responses in sensory neurons have revealed signaling and transcriptional mechanisms that increase their intrinsic regenerative capacity. However, the extent to which satellite glial cells (SGC), which completely surround the neuronal soma contribute to these responses remains unexplored. Using single cell RNA-seq, we defined the transcriptional profile of SGC in naïve and injured conditions and identified Fabp7, also known as BLBP, as a novel marker of SGC. We report that nerve injury elicits gene expression changes in SGC, which are mostly related to lipid metabolism, specifically fatty acid synthesis and the peroxisome proliferator-activated receptor (PPAR) signaling. Conditional deletion of Fatty acid synthase (Fasn), the key enzyme in de novo fatty acid synthesis, specifically in SGC, impairs axon regeneration. Treatment with fenofibrate, a PPARa agonist, rescues the impaired regeneration, suggesting that PPRAa, which belongs to a family of lipid regulated transcription factors, functions downstream of fatty acid synthesis in SGC to promote axon regeneration. These results unravel fatty acid synthesis in SGC as a fundamental novel mechanism mediating axon regeneration in mature peripheral nerves.
2020-08-23 | GSE139103 | GEO
Project description:Peripheral nerve injury (PNI) could transform primary somatosensory neurons into regenerative state. However, details of transcriptomic changes associated to nerve regeneration of somatosensory neurons maintain unclear. 10x single-cell RNA sequencing (scRNA-seq) was conducted on mice dorsal root ganglia (DRG) cells after early stage of nerve injury on day 3 post-constriction chronic injury (CCI). We observed that a novel CCI-induced neuronal population (CIP) emerged and expressed high levels of activating transcription factor (Atf3), a neuronal injury marker. CIP neurons highly expressed regenerative associated genes (RAGs) and were enriched in regeneration-related gene ontology (GO) terms, suggesting these neurons could be a pro-regenerative population. Moreover, intercellular communication networks showed that CIP neurons have a close communication to satellite glia cells (SGCs) and specifically transmitted strong Fgf3-Fgfr1 signaling to SGCs, which could initiate regeneration-associated transcriptional changes of SGCs. This study also confirmed that the regenerative progress occurred at the early stage of nerve injury because immunohistochemistry showed the expression of ATF3 significantly increased since day 3 post-CCI and decreased at 1 month. Our bioinformatics analysis at single-cell resolution advances the knowledge of regenerative dynamic transcriptional changes of DRG cells after injuries and their underlying molecular mechanisms.
2024-02-09 | GSE255014 | GEO
Project description:<p>Lysosomes are key cellular organelles that metabolize extra- and intra-cellular substrates. Alterations in lysosomal metabolism are implicated in aging-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate aging remains unclear. Here, we report a fat-to-neuron lipid signaling pathway induced by lysosomal metabolism and its longevity promoting role in <em>Caenorhabditis elegans</em>. We discovered that induced lysosomal lipolysis in peripheral fat storage tissue up-regulates the neuropeptide signaling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation is mediated by a 47 specific polyunsaturated fatty acid, dihomo-gamma-linolenic acid (DGLA) and LBP-3 lipid chaperone protein transporting from the fat storage tissue to neurons. LBP-3 binds to DGLA, and acts through NHR-49 nuclear receptor and NLP-11 neuropeptide in neurons to extend lifespan. These results reveal lysosomes as a signaling hub to coordinate metabolism and aging, and lysosomal signaling mediated inter-tissue communication in promoting longevity.</p>
2022-05-06 | MTBLS4654 | MetaboLights
Project description:Website for easy exploration of the data: https://rna-seq-browser.herokuapp.com/# For the first time, we here characterize the transcriptional signature of satellite glial cells (SGCs) in a nerve injury-paradigm by isolating SGCs from mouse dorsal root ganglia (DRGs) after peripheral nerve injury followed by next generation RNA sequencing (RNA-seq). We found that SGCs regulate their gene expression differently at 3 days and 14 days after peripheral nerve injury suggesting that they change their function over time. At both time points, we found downregulation of several genes linked to cholesterol. After 14 days we further detect regulation of genes linked to the immune system (MHC protein complex and leukocyte migration). The SGC RNA-seq data is accompanied by RNA-seq of purified nociceptors from injured (partial sciatic nerve ligation) or sham (ipsi after sham operation or contra after partial sciatic nerve ligation) L3-L5 DRGs.
2020-01-22 | GSE120284 | GEO
Project description:Dorsal root ganglia (DRG) play a crucial role in processing sensory information, making it essential to understand their development. Here, we construct a single-cell spatiotemporal transcriptomic atlas of human embryonic DRG. This atlas reveals the diversity of cell types and highlights the extrinsic signaling cascades and intrinsic regulatory hierarchies that guide cell fate decisions, including neuronal/glial lineage restriction, sensory neuron differentiation and specification, and the formation of neuron-satellite glial cell (SGC) unit. Additionally, we identify a human-enriched NTRK3+/DCC+ nociceptor subtype, which is involved in multimodal nociceptive processing. Mimicking the programmed activation of signaling pathways in vivo, we successfully establish functional human DRG organoids and underscore the critical roles of transcriptional regulators in the fate commitment of unspecialized sensory neurons (uSNs). Overall, our research elucidates the multilevel signaling pathways and transcription factor (TF) regulatory hierarchies that underpin the diversity of somatosensory neurons, emphasizing the phenotypic distinctions in human nociceptor subtypes.
2024-09-05 | GSE245310 | GEO
Project description:Although DNA methylation plays a critical role in the development and function of mammalian central nervous system (CNS), its role in peripheral neurons has not been elucidated. To address this issue, we produced conditional knockout mice (CKO) specifically deleting the gene for maintenance DNA methyltransferase 1 (Dnmt1) during the development of neural crest cells. Despite global hypomethylation in the embryonic dorsal root ganglion (DRG) of the CKO mice, the number of sensory neurons was relatively unaffected. However, expression of many genes required for sensory neuron development was altered in embryonic mutant DRG, including down-regulation of Runx1 and TrkA genes as well as up-regulation of Id1 and Dtx1, two negative regulators for neurogenesis. Accompanied with the downregulation of an NGF receptor TrkA, the peripheral axonal projection and the branching of sensory neurons were impaired. Furthermore, the expression of the neuropeptide Galanin and several vanilloid receptors such as TrpV1 and TrpM8 were not detected in the DRG of the CKO mice during late embryonic and neonatal stages, suggesting that DNA methylation regulates the differentiation program for a subset of nociceptive sensory neurons. Taken together, our findings suggest that through transcriptional regulation of key developmental genes in sensory neurons, DNA methylation play a key role in the control of the axonal projection and fate specification of peripheral sensory neurons. We compared gene expression patterns in Wildtype and DNA methylation deficient (Wnt1-cre; Dnmt1 mutant) mouse dorsal cortex. We performed 4 replicates using different each individual mouse strain. The Sample GSM565172 table is the average log ratio for the 4 replicatesArrays were performed.
2011-12-01 | E-GEOD-23530 | biostudies-arrayexpress
Project description:After an injury in the adult mammalian central nervous system, lesioned axons fail to regenerate. This failure to regenerate contrasts with the remarkable potential of axons to grow following an injury in the peripheral nervous system. Peripheral sensory neurons with cell soma in dorsal root ganglia (DRG) switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Decades of research have focused on the signaling pathways elicited by injury in sensory neurons and in Schwann cells that insulate axons as central mechanisms regulating nerve repair. However, neuronal microenvironment is far more complex and is composed of multiple cell types including endothelial, immune and glial cells. Whether the microenvironment surrounding neuronal soma contribute to the poor regenerative outcomes following central injuries remains largely unexplored. To answer this question, we performed a single cell transcriptional profiling of the DRG neuronal microenvironment response to peripheral and central injuries. In dissecting the roles of the microenvironment contribution, we have focused on a poorly studied glia population of Satellite Glial Cells (SGC) surrounding the neuronal cell soma. Upon a peripheral injury, SGC contribute to axon regeneration via Fatty acid synthase (Fasn)-PPARα signaling pathway. Our analysis reveals that in response to central injuries, SGC do not activate the PPAR signaling pathway. However, induction of this pathway with fenofibrate, an FDA- approved PPARα agonist used for dyslipidemia treatment, rescued axon regeneration following an injury to the central nerves. Collectively, our results uncovered a previously unappreciated role of the neuronal microenvironment differential response in central and peripheral injuries.
2021-09-12 | GSE158892 | GEO
Project description:Aim: Dorsal root ganglion neuron-derived immortal cell lines including ND7/23 and F-11 cells have been used extensively as in vitro model systems of native peripheral sensory neurons. However, while it is clear that some sensory neuron-specific receptors and ion channels are present in these cell lines, a systematic comparison of the molecular targets expressed by these cell lines with intact peripheral neurons is lacking. Methods: we examined the expression of RNA transcripts in the human neuroblastoma-derived cell line, SH-SY5Y, and two dorsal root ganglion hybridoma cell lines, F-11 and ND7/23, using Illumina next-generation sequencing. Results: The expression profile of these three cell lines did not resemble any specific dorsal root ganglion neuron subclass. The cell lines lacked many markers for nociceptive sensory neurons, such as the transient receptor potential V1 gene, but expressed markers for both myelinated and unmyelinated neurons. Conclusion: This paper provides insights into the receptor repertoire expressed in common dorsal root ganglion neuron-derived cell lines, and illustrates the limits and potentials of these cell lines as tools for neuropharmacological exploration.
2016-05-01 | GSE75811 | GEO
Project description:Trigeminal ganglion (TG) is the first station of sensory pathways in the orofacial region. The TG neurons communicate with satellite glial cells (SGCs), macrophages and other cells forming a functional unit that is responsible for processing of orofacial sensory information. Purinergic signaling, one of the most widespread autocrine and paracrine pathways, plays a crucial role in intercellular communication. The multidirectional action of purinergic signaling in different cell types contributes to the neuromodulation and orofacial sensation. To fully understand the purinergic signaling in these processes, it is essential to determine the shared and unique expression patterns of genes associated with purinergic signaling in different cell types. Here, we performed single-cell RNA sequencing of 22,969 cells isolated from normal mouse TGs. We identified 18 distinct cell populations, including 6 neuron subpopulations, 3 glial subpopulations, 7 immune cell subpopulations, fibroblasts, and endothelial cells. We also revealed the transcriptional features of genes associated with purinergic signaling, including purinergic receptors, extracellular adenosine triphosphate (eATP) release channels, eATP metabolism-associated enzymes, and eATP transporters) in each cell type. Our results have important implications for understanding and predicting the cell type-specific roles of the purinergic signaling in orofacial signal processing in the trigeminal primary sensory system.
2022-10-12 | GSE213105 | GEO