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Single-cell transcriptomic analysis links non-myelinating Schwann cells to pro-inflammatory response in the lung [bulk RNA-Seq]

ABSTRACT: The lung is a barrier tissue with constant exposure to the inhaled environment. Therefore, innate immunity against particulates and pathogens is of critical importance to maintain tissue homeostasis. While the lung harbors both myelinating and non-myelinating Schwann cells (NMSCs), NMSCs represent the abundant Schwann cell (SC) population in the lung. However, their contribution to lung physiology remains largely unknown. Here, we used the human glial fibrillary acidic protein promoter (GFAP) driving tdTomato expression in mice to identify SCs in the peripheral nervous system (PNS) and determine their location within the lung. Single-cell transcriptomic analysis revealed the existence of two NMSC populations (NMSC1 and NMSC2) that may participate in pathogen recognition. We demonstrated that these pulmonary SCs produce chemokines and cytokines upon lipopolysaccharide (LPS) stimulation using in vitro conditions. Furthermore, we challenged mouse lungs with LPS and found that NMSC1 exhibits an enriched pro-inflammatory response among all SC subtypes. Collectively, these findings define the molecular profiles of lung SCs and suggest a potential role for NMSCs in lung inflammation.

ORGANISM(S): Mus musculus

PROVIDER: GSE235905 | GEO | 2023/06/28

REPOSITORIES: GEO

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Single-cell transcriptomic analysis links non-myelinating Schwann cells to pro-inflammatory response in the lung [scRNA-seq]

Project description:The lung is a barrier tissue with constant exposure to the inhaled environment. Therefore, innate immunity against particulates and pathogens is of critical importance to maintain tissue homeostasis. While the lung harbors both myelinating and non-myelinating Schwann cells (NMSCs), NMSCs represent the abundant Schwann cell (SC) population in the lung. However, their contribution to lung physiology remains largely unknown. Here, we used the human glial fibrillary acidic protein promoter (GFAP) driving tdTomato expression in mice to identify SCs in the peripheral nervous system (PNS) and determine their location within the lung. Single-cell transcriptomic analysis revealed the existence of two NMSC populations (NMSC1 and NMSC2) that may participate in pathogen recognition. We demonstrated that these pulmonary SCs produce chemokines and cytokines upon lipopolysaccharide (LPS) stimulation using in vitro conditions. Furthermore, we challenged mouse lungs with LPS and found that NMSC1 exhibits an enriched pro-inflammatory response among all SC subtypes. Collectively, these findings define the molecular profiles of lung SCs and suggest a potential role for NMSCs in lung inflammation.

2023-06-28 | GSE235904 | GEO

SNAT - RNA sequencing of sorted Schwann cells as a single mixed population, enriched in myelinating Schwann cells, or enriched in not-myelinating Schwann cells

Project description:RNA sequencing of sorted mouse Schwann cells expressing YFP due to P0Cre-mediated recombination. The plotting of side scatter versus eYFP fluorescence generates 2 semi-detached eYFP+ clouds of cells, which further enables the enriched selection of myelinating Schwann cells, and of not-myelinating Schwann cells.

2021-04-22 | GSE137947 | GEO

Dynamic gene expression in Schwann cell for regulating myelination

Project description:To obtain the dynamic gene expression of myelinating Schwann cells, we have employed gene expression profiling microarray as a discovery platform to analyze the gene expression of Schwann cells in different stages of myelination in an DRG neuron and SC co-culture myelinating model. Rat Schwann cells and dorsal root ganglion (DRG) neurons were cocultured and induced myelination in DMEM medium containing 15% FBS, 50 ng/ml NGF and 50 μg/ml L-ascorbic acid for 21d. During the co-cultivation, myelinating SCs at different stages dissected by Laser microdissection (LMD) in myelination model (i.e. co-culture 1d, 3d, 7d, 14d, 21d), the Schwann cells without co-culture as control samples (i.e. co-culture 0d). The results from Euclidean distance matrix, principal component analysis, and hierarchical clustering indicated that 2 nodal transitions in temporal gene expressions could segregate 3 distinct transcriptional phases within the period of DRG/SC co-culture 21 days. The 3 phases were designated as “premyelination”, “myelination”, and “mature phase”, respectively, by referring to morphological observation of post co-culture changes and gene ontology (GO) analysis.

2022-09-21 | GSE163132 | GEO

Scalable generation of Schwann cell precursors from human pluripotent stem cells

Project description:Schwann cells (SCs) are an absolute prerequisite for development of effective treatment of myelin disorders and nerve injuries. However, human sources of functional, myelinating SCs are extremely limited. Here, we have developed a novel, efficient strategy for producing directly an unlimited supply of functional human SCs via successful derivation of expandable Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs) (hPSC-SCPs). Functional and molecular characteristics of SCs from hPSC-SCPs (hPSC-SCP-SCs) appeared to be similar to those of authentic Schwann cells. As a novel therapeutic target, transplanted hPSC-SCP-SCs effectively promoted axonal regeneration through directly myelinating regenerated-axons in sciatic nerve injured mice. Here, we present hPSC-SCPs and hPSC-SCP-SCs as an outstanding resource to use for investigating human Schwann cell pathology and biology and for translational approaches to PNS and CNS repair and regeneration.

2017-08-15 | GSE95004 | GEO

Redefining the heterogeneity of peripheral nerve cells in health and autoimmunity

Project description:Peripheral nerves contain axons and their enwrapping glia cells named Schwann cells (SC) that are either myelinating or non-myelinating (nmSC). Our understanding of other cells in the peripheral nervous system (PNS) remains limited. Here, we provide an unbiased single-cell transcriptomic characterization of the non-diseased rodent PNS. We identified and independently confirmed novel markers of previously underappreciated nmSC and nerve-associated fibroblasts. We also found and characterized two distinct populations of nerve-resident homeostatic myeloid cells that transcriptionally differed from central nervous system microglia. In a model of chronic autoimmune neuritis, homeostatic myeloid cells were outnumbered by infiltrating lymphocytes which modulated the local cell-cell interactome and induced a specific transcriptional response in glia cells. This response was partially shared between the peripheral and central nervous system glia identifying common immunological features across different parts of the nervous system. Our study thus identifies novel subtypes and cell-type markers of PNS cells and a partially conserved autoimmunity module induced in glia cells.

2020-04-01 | GSE142541 | GEO

Schwann cell plasticity regulates neuroblastic tumor cell differentiation

Project description:The remarkable plasticity of Schwann cells (SCs) is essential for nerve regeneration but also contributes to neuropathies and cancer progression. It has not yet been investigated whether the adaptive potential of SCs is manifested in stromal, tumor associated SCs characteristically found within a benign subtype of neuroblastic tumors (NBTs). We here performed transcriptome profiling of human NBTs, rich and poor in SC stroma, as well as human injured nerves, rich in repair SCs, revealing that stromal SCs exhibit a repair SC characteristic gene expression signature. In turn, primary repair SCs had a pro-differentiating and anti-proliferative effect on NBT cell lines after direct and trans-well co-culture. Within the pool of secreted stromal/repair SC factors, we identified EGFL8, a matricellular protein with so far undescribed function, to induce neuronal differentiation of aggressive NBT cells. EGFL8 expression further correlated with favorable tumor stage and increased patient survival. Our findings suggest that stromal SCs exert nerve repair associated functions in the tumor-environment and underline the therapeutic value of SC-derived factors for aggressive, SC stroma-poor NBTs.

2021-01-13 | PXD018267 | Pride

Schwann cell plasticity regulates neuroblastic tumor cell differentiation - phosphoproteomics

2021-01-04 | PXD022217 | Pride

Matrix metalloproteinase-9 and TIMP-1 in peripheral nerve: Implications for myelin formation

Project description:Remyelination is a key step in functional nerve regeneration performed by Schwann cells (SC). We have demonstrated that matrix metalloproteinase (MMP)-9 is a major regulator of signal transduction and phenotypic switching in SCs. Herein, genome-wide transcriptional profiling, followed by Ingenuity Pathway Analysis revealed the MMP-9 signaling network and its endogenous inhibitor, TIMP-1, among the top induced genes of the injured sciatic nerve, that co-distributed with MMP-9 in myelinating SCs and the paranodal/nodal areas of myelinated fibers. Homo- and heterodimers of the active and proMMP-9 were purified from injured nerves using gelatin-sepharose. MMP-9 gene deletion increased the number of immature, GFAP+ mSC and post-mitotic cell counts that correlate with shorter myelin internodes in remyelinated fibers lacking MMP-9. MMP-9 is essential to nodal clustering of voltage-gated Na+ (Nav) channels. MMP inhibitor therapy diminished the expression of Nav 1.7 and 1.8. These data established the essential role of MMP-9 in guiding SC differentiation toward myelin production and in molecular assembly of the myelin domains. Modification of Nav channels in myelinated fibers may thus provide an important therapeutic approach for a number of facilitates regeneration and attenuated neuropathic pain. Gene expression profiling of total RNAs extracted from murine sciatic nerves, dorsal root ganglion and spinal cords at day 1 and day 5 post injury.

2012-02-28 | E-GEOD-33454 | biostudies-arrayexpress

SNAT - RNA sequencing of sorted Schwann cells as a single mixed population, enriched in myelinating Schwann cells, or enriched in not-myelinating Schwann cells

Project description:SNAT - RNA sequencing of sorted Schwann cells as a single mixed population, enriched in myelinating Schwann cells, or enriched in not-myelinating Schwann cells

| PRJNA573929 | ENA

Schwann cell plasticity regulates neuroblastic tumor cell differentiation

2020-12-23 | GSE147635 | GEO

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