Project description:Although satellite glial cells (SGCs) are among the most abundant non-neuronal cells in dorsal root ganglia (DRG), little is known about their heterogenity and functions. We used single cell RNA sequencing (scRNA-seq) to analyze the heterogenity and unique functions of SGCs.
Project description:Satellite glia are the major glial type found in ganglia of the peripheral nervous system that wrap around cell bodies of sympathetic and sensory neurons that are very diverse. Other than their close physical association with peripheral neurons, little is known about this glial population. Here, we performed single cell RNA sequencing analysis and identified five different populations of satellite glia from sympathetic and sensory ganglia. We identify three shared populations of satellite glia enriched in immune-response genes, immediate-early genes and ion channels/ECM-interactors, respectively. Sensory- and sympathetic-specific satellite glia are differentially enriched for modulators of lipid metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Further, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals remarkable heterogeneity of satellite glia in the peripheral nervous system.
Project description:G protein-coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR, and its function remains largely unknown. Here we report that Gpr37l1 and GPR37L1 are among the most highly expressed GPCR transcripts in mouse and human dorsal root ganglia (DRGs) and are selectively expressed in satellite glial cells (SGCs). Peripheral neuropathy following PTX-induced pain resulted in a downregulation of GPR37L1 plasma membrane expression in DRGs. Transgenic mice with Gpr37l1 deficiency exhibited impaired resolution of neuropathic pain symptoms following PTX-induced pain, whereas overexpression of Gpr37l1 in mouse DRGs reversed pain. GPR37L1 regulates the surface expression and function of these potassium channels. Thus, GPR37L1 in SGCs offers a new target for neuropathy protection and pain control.
Project description:Sensory neuron soma and non-neuronal cells in adult dorsal root ganglia (DRG) derive from multipotent neural crest cells. Satellite glial cells (SGCs), which surround neuronal soma, were suggested to retain developmental potential, but the precise molecular identity of progenitor cells in the adult DRG remains undefined. To address this question, we assembled a comprehensive single-cell transcriptomic atlas by integrating over 200,000 DRG and sciatic nerve transcriptomes across multiple studies and injury paradigms. High-resolution clustering resolved 26 cell types and demonstrated significant transcriptional heterogeneity within SGCs and Schwann cells, including repair and reactive sub-states. Crucially, we identified two distinct populations of progenitor cells that reflect different states in the progenitor trajectory. Functionally, progenitor cell numbers significantly increase after injury, and endothelin signaling regulates glial cell proliferation early in development. This integrated DRG and peripheral nerve cell atlas represents an essential resource for exploring new features of the peripheral nervous system.
Project description:The recent advance in single cell RNAseq technologies has enabled a new approach to investigate satellite glial cells (SGCs). Here we publish a dataset from mice subjected to sciatic nerve injury as well as a dataset from dorsal root ganglia cells after 3 days in culture. We use a meta-analysis approach to compare the injury response with that in other published datasets and conclude that SGCs share a common signature following sciatic nerve crush and sciatic ligation, involving transcriptional regulation of cholesterol biosynthesis. We also observed a considerable transcriptional change when culturing SGCs, suggesting that some differentiate into a specialised in vitro state, while others start resembling Schwann cell-like precursors.
Project description:Neuropathic pain, affecting 10% of the general population, poses a significant socioeconomic burden that current treatment options cannot sufficiently cover. While pain naturally resolves in some patients, the mechanisms driving this process remain elusive. we hypothesized that pain resolution modulates multicellular interactions of neurons, satellite glial cells (SGCs), and local macrophages within the dorsal root ganglia (DRGs). Therefore, we aimed to identify molecular and cellular processes that characterize ongoing pain resolution. With behavioral tests, we determined a 50% improvement of the pain phenotype to capture ongoing mechanisms of pain resolution. We expect to see dysregulated signaling mediators in the DRG, as well as channels and components influencing hypersensitivity, as well as regulation of an immune and inflammatory phenotype. Comparing the ipsilateral sides during hypersensitvity and pain resolution, we aim to elucidate pathways that characterize the resolution phase. Based on prior knowledge and imaging data, we expected to initially see a strong immune phenotype, with differences between male and female rats during pain resolution, potentially reflecting a difference in pain prevalence between sexes in the clinic. Pathway analysis of the bulk RNA data confirmed an ongoing immune phenotype in female rats as opposed to males. Top regulated factors after CCI, include many mediators such as NPY, VIP, Gal, IL24 and IL6. Biological processes associated with pain resolution included G-protein coupled receptor signaling, synaptic transmission and regulation of the membrane potential.