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Synaptic Schwann cells: specific labeling reveals unique cellular and molecular features

ABSTRACT: Perisynaptic Schwann cells (PSCs) are specialized, non-myelinating, synaptic glia of the neuromuscular junction (NMJ), that participate in synapse development, function, maintenance, and repair. The study of PSCs has relied on an anatomy-based approach, as the identities of cell-specific PSC molecular markers have remained elusive. This limited approach has precluded our ability to isolate and genetically manipulate PSCs in a cell specific manner. We have identified neuron-glia antigen 2 (NG2) as a unique molecular marker of S100β+ PSCs in skeletal muscle. NG2 is expressed in Schwann cells already associated with the NMJ, indicating that it is a marker of differentiated PSCs. Using a newly generated transgenic mouse in which PSCs are specifically labeled, we show that PSCs have a unique molecular signature that includes genes known to play critical roles in PSCs and synapses. These findings will serve as a springboard for revealing drivers of PSC differentiation and function.

ORGANISM(S): Mus musculus

PROVIDER: GSE152774 | GEO | 2020/06/19

REPOSITORIES: GEO

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Cellular and molecular evidence that synaptic Schwann cells contribute to aging of mouse neuromuscular junctions

Project description:Age-induced degeneration of the neuromuscular junction (NMJ) is associated with motor dysfunction and muscle atrophy. While the impact of aging on the NMJ pre- and postsynapse is well-documented, little is known about the changes perisynaptic Schwann cells (PSCs), the synaptic glia of the NMJ, undergo during aging. Here, we examined PSCs in young, middle-aged, and old mice in three muscles with different susceptibility to aging. Using light and electron microscopy, we found that PSCs acquire age-associated cellular features either prior to or at the same time as the onset of NMJ degeneration. Notably, we found that aged PSCs fail to completely cap the NMJ even though they are more abundant in old compared to young mice. We also found that aging PSCs form extensions that guide axon terminal sprouts away from innervated NMJs. We next profiled the transcriptome of PSCs and other Schwann cells (SCs) to identify mechanisms altered in aged PSCs. This analysis revealed that aged PSCs acquire a transcriptional pattern that promotes phagocytosis that is absent in other SCs. It also showed that aged PSCs upregulate unique pro-inflammatory molecules compared to other aged SCs. Interestingly, neither synaptogenesis genes nor genes that are typically upregulated by repair SCs were induced in aged PSCs or other SCs. These findings provide insights into cellular and molecular mechanisms that could be targeted in PSCs to stave-off the deleterious effects of aging on NMJs.

2023-11-22 | GSE222631 | GEO

Transcriptome analysis of neuromuscular junction during degeneration and regeneration of axon terminal

Project description:The neuromuscular junction (NMJ) is a specialized tripartite synapse composed of the motor axon terminal, covered by perisynaptic Schwann cells (PSCs), and the muscle fibre, separated by a basal lamina. It is exposed to different kind of injures such as mechanical traumas, pathogens including neurotoxins, and neuromuscular diseases such as amyotrophic lateral sclerosis and immune-mediated disorders, and has retained throughout vertebrate evolution an intrinsic ability for repair and regeneration, at variance from central synapses1. Following peripheral nerve injury, an intense but poorly defined crosstalk takes place at the NMJ among its components, functional to nerve terminal regeneration. To identify crucial factors released by PSCs and the muscle to induce nerve regrowth, we performed a transcriptome analysis of the NMJ at different time points after injection of -latrotoxin, a presynaptic neurotoxin isolated from the venom of the black widow spider. This toxin is a simple and controlled method to induce an acute, localized and reversible nerve terminal degeneration not blurred by inflammation, and can help to identify molecules involved in the intra- and inter-cellular signalling governing NMJ regeneration.

2017-05-30 | E-MTAB-5730 | biostudies-arrayexpress

NG2 glia-derived GABA release tunes inhibitory synapses and contributes to anxiety-like behavior in chronic social defeat stress

Project description:NG2 glia, also known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development. In contrast to other glial cell types, the most intriguing aspect of NG2 glia is their ability to directly sense synaptic inputs from neurons. However, whether this synaptic interaction is bidirectional or unidirectional, or its physiological relevance has not yet been clarified. Here, we report that NG2 glia form synaptic complexes with hippocampal interneurons and that selective photostimulation of NG2 glia (expressing channelrhodopsin-2) functionally drives GABA release and enhances inhibitory synaptic transmission onto proximal interneurons in a microcircuit. The mechanism involves GAD67 biosynthesis and VAMP-2 containing vesicular exocytosis. Further, behavioral assays demonstrate that NG2 glia photoactivation triggers an anxiety-like behavior in vivo and induces anxiety-like behavior in a mouse model of chronic social defeat stress.

2020-11-24 | GSE162049 | GEO

Single cell expression profiling of NG2 cell lineage from adult mice cortex three days after focal cerebral ischemia

Project description:Ischemic stroke is a serious medical condition that leads to neurological symptoms such as loss of motor and cognitive function. Focal cerebral ischemia (FCI) occurs due to interruption of blood supply to the site of injury, leading to the death of brain cells. Cells carrying Neural-glial antigen 2 (NG2) include glial cells serving primarily as olidogendrocyte precursors and a portion of pericytes. NG2 glia proliferate rapidly after ischemia and migrate to the site of injury, participate with astrocytes in glial scar formation, and contribute to the regeneration of the brain tissue. The ability of NG2 glia to differentiate into a different cell type than oligodendrocytes has been described but is still controversial. We therefore isolated NG2 cells and their derivatives labeled with tdTomato red fluorescent protein from the cortex of Rosa26-tdTomato/Cspg4-CreERT2 mice three days after middle cerebral artery occlusion (MCAO). Sham-operated animals were used as healthy controls (CTRL). We aimed to identify NG2 cell types and their derivatives in the cortex of healthy and ischemic mice and determine their incidence as well as characteristic gene expression.

2023-09-21 | E-MTAB-11967 | biostudies-arrayexpress

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2014-10-03 | E-GEOD-43770 | biostudies-arrayexpress

Expression data from RLT-PSC, human pancreatic stellate cell lineage

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2014-08-10 | E-GEOD-59953 | biostudies-arrayexpress

KLF4 binding is involved in the organization and regulation of 3D enhancer networks during acquisition and maintenance of pluripotency.

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2019-09-03 | PXD014631 | Pride

Identification of Latrophilin-2, a Specific Cell-surface Marker for Cardiac Progenitor Cells, and its Functional Significance in Heart Development [RNA-Seq]

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2018-12-31 | GSE102973 | GEO

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2014-06-02 | E-MTAB-2061 | biostudies-arrayexpress

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2013-01-17 | E-GEOD-43496 | biostudies-arrayexpress

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