Identification of adhesion‑associated DNA methylation patterns in the peripheral nervous system

Abstract

Schwann cells are unique glial cells in the peripheral nervous system. These cells provide a range of cytokines and nutritional factors to maintain axons and support axonal regeneration. However, little is known concerning adhesion-associated epigenetic changes that occur in Schwann cells after peripheral nerve injury (PNI). In the present study, adhesion-associated DNA methylation biomarkers were assessed between normal and injury peripheral nerve. Specifically, normal Schwann cells (NSCs) and activated Schwann cells (ASCs) were obtained from adult Wistar rats. After the Schwann cells were identified, proliferation and adhesion assays were used to assess differences between NSCs and ASCs. Methylated DNA immunoprecipitation-sequencing and bioinformatics analysis were used to identify and analyze the differentially methylated genes. Reverse transcription-quantitative PCR was performed to assess the expression levels of adhesion-associated genes. In the present study, the proliferation and adhesion assays demonstrated that ASCs had a more robust proliferative activity and adhesion compared with NSCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify methylation-associated biological processes and signaling pathways. Protein-protein interaction network analysis revealed that Fyn, Efna1, Jak2, Vav3, Flt4, Epha7, Crk, Kitlg, Ctnnb1 and Ptpn11 were potential markers for Schwann cell adhesion. The expression levels of several adhesion-associated genes, such as vinculin, BCAR1 scaffold protein, collagen type XVIII α1 chain and integrin subunit β6, in ASCs were altered compared with those in NSCs. The current study analyzed adhesion-associated DNA methylation patterns of Schwann cells and identified candidate genes that may potentially regulate Schwann cell adhesion in Wistar rats before and after PNI.

ALK signalling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition

“…Hypomethylated regions were less frequent but still present following ATRi treatment (Fig. 7B) and cluster analysis revealed in total five significant clusters (Benjamini < 10 -6 ) all involving cell adhesion, in keeping with previous reports of a link between adhesive properties of Schwann cells with levels of DNA methylation 33 . Collectively, our findings provide compelling evidence that ATR inhibition induces widespread hypermethylation in treated tumours, which is concurrent with the observed dedifferentiation process towards a Schwann cell-like phenotype.…”

Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model

“…However, additional noteworthy collagens were higher in the other clusters, perhaps highlighting a specialized role for each group. COL5A3 , which promotes Schwann cell adhesion and neurite growth ( 66 , 67 ), was significantly higher in Fibroblasts 6. COL4A2 was also enriched in Fibroblasts 6; Type IV collagens are localized to basement membranes and surround Schwann cells to promote axonal growth ( 66 ).…”

“…ECM composition containing Type I collagens might be less conducive to tumor growth. In contrast, collagens such as COL4A2 ( 66 ) , COL5A3 ( 66 , 67 ), and COL15A1 ( 68 , 69 ), which play roles in axonal growth, Schwann cell adhesion and neurite growth, or are critical components in nerve regeneration, were enriched in fibroblast groups primarily found in the two dpNFs ( Figure 7B ) .…”