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

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

PROVIDER: PRJNA573929 | ENA |

REPOSITORIES: ENA

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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

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.

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

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Nucleoporin Seh1 Maintain Schwann Cell Homeostasis by Regulating Genome Stability and Necroptosis

Project description:Schwann cells play critical roles in peripheral neuropathies, however, the regulatory mechanisms of their homeostasis remain largely unknown. Here we show that nucleoporin Seh1, a component of nuclear pore complex, is important for Schwann cell homeostasis and loss of Seh1 led to necroptosis of non-myelinating Schwann cell and degeneration of sensory neurons. While myelinogenesis, myelinating Schwann cell, and wrapped large fibers were not affected, mice with depletion of Seh1 in Schwann cell lineage developed progressive reduction of non-myelinating Schwann cells in sciatic nerves, followed by the degeneration of unmyelinated small sensory fibers and malfunction of the sensory system. Mechanistically, Seh1 safeguards genome stability by mediating the interaction between SETDB1 and KAP1. The disrupted interaction after ablation of Seh1 derepresses endogenous retroviruses, which triggers ZBP1-dependent necroptosis in non-myelinating Schwann cells. Collectively, our results reveal that Seh1 is required for homeostasis of Schwann cells and suggest that decrease of nucleoporins as aging may participate in the pathogenesis of periphery neuropathies.

2023-01-03 | GSE222015 | GEO

Schwann cell regulation by NR2F2 using Cut&Run

Project description:We focused on NR2F1 and NR2F2 (CoupTF1/CoupTF2) since they are expressed from neural crest through Schwann cell maturity, and found that knockdown of nuclear receptors Nr2f1 and Nr2f2 in primary Schwann cells downregulated genes such as Myelin Basic Protein (Mbp), Desert Hedgehog (Dhh), and N-Myc Downstream Regulated 1 (Ndrg1). In this study, we have elucidated a NR2F-regulated target gene network in Schwann cells, which revealed enrichment for non-myelinating Schwann cell genes. We used Cut&Run in S16 Schwann cells to show novel, genome-wide binding sites of NR2F1/2 and downstream transcription factors, YY1, SREBP1, Retinoid X Receptor (RXRG) and TEA-Domain factor (TEAD1). Our study elucidates the transcriptional cooperation that forms unique enhancer landscapes and the regulatory network that targets non-myelinating Schwann cells.

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Direct conversion of rodent fibroblasts into myelinating induced Schwann cells

Project description:Transcriptome analysis of rodent fibroblast-derived induced Schwann cells

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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.

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Project description:SNAT - Single cell RNA sequencing of mouse sorted Schwann cells at postnatal day 5 (P5)

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SNAT - Single cell RNA sequencing of mouse sorted Schwann cells at postnatal day 1 (P1)

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