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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 ?1 chain and integrin subunit ?6, 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.

SUBMITTER: Zuo S

PROVIDER: S-EPMC7706384 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Zuo Shanhuai S Shi Guidong G Fan Jianchao J Fan Baoyou B Zhang Xiaolei X Liu Shen S Hao Yan Y Wei Zhijian Z Zhou Xianhu X Feng Shiqing S

Experimental and therapeutic medicine 20201118 1

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 ...[more]

PMID: 33273976

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Project description:BACKGROUND:Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition involving multiple organ systems and characterized by persistent/relapsing debilitating fatigue, immune dysfunction, neurological problems, and other symptoms not curable for at least 6 months. Disruption of DNA methylation patterns has been tied to various immune and neurological diseases; however, its status in ME/CFS remains uncertain. Our study aimed at identifying changes in the DNA methylation patterns that associate with ME/CFS. METHODS:We extracted genomic DNA from peripheral blood mononuclear cells from 13 ME/CFS study subjects and 12 healthy controls and measured global DNA methylation by ELISA-like method and site-specific methylation status using Illumina MethylationEPIC microarrays. Pyrosequencing validation included 33 ME/CFS cases and 31 controls from two geographically distant cohorts. RESULTS:Global DNA methylation levels of ME/CFS cases were similar to those of controls. However, microarray-based approach allowed detection of 17,296 differentially methylated CpG sites in 6,368 genes across regulatory elements and within coding regions of genes. Analysis of DNA methylation in promoter regions revealed 307 differentially methylated promoters. Ingenuity pathway analysis indicated that genes associated with differentially methylated promoters participated in at least 15 different pathways mostly related to cell signaling with a strong immune component. CONCLUSIONS:This is the first study that has explored genome-wide epigenetic changes associated with ME/CFS using the advanced Illumina MethylationEPIC microarrays covering about 850,000 CpG sites in two geographically distant cohorts of ME/CFS cases and matched controls. Our results are aligned with previous studies that indicate a dysregulation of the immune system in ME/CFS. They also suggest a potential role of epigenetic de-regulation in the pathobiology of ME/CFS. We propose screening of larger cohorts of ME/CFS cases to determine the external validity of these epigenetic changes in order to implement them as possible diagnostic markers in clinical setting.

Project description:Hemangioblastomas (HBs) of the central nervous system are highly vascular neoplasms that occur sporadically or as a manifestation of von Hippel-Lindau (VHL) disease. Despite their benign nature, HBs are clinically heterogeneous and can be associated with significant morbidity due to mass effects of peritumoral cysts or tumor progression. Underlying molecular factors involved in HB tumor biology remain elusive. We investigated genome-wide DNA methylation profiles and clinical and histopathological features in a series of 47 HBs from 42 patients, including 28 individuals with VHL disease. Thirty tumors occurred in the cerebellum, 8 in the brainstem and 8 HBs were of spinal location, while 1 HB was located in the cerebrum. Histologically, 12 HBs (26%) belonged to the cellular subtype and exclusively occurred in the cerebellum, whereas 35 HBs were reticular (74%). Unsupervised clustering and dimensionality reduction of DNA methylation profiles revealed two distinct subgroups. Methylation cluster 1 comprised 30 HBs of mainly cerebellar location (29/30, 97%), whereas methylation cluster 2 contained 17 HBs predominantly located in non-cerebellar compartments (16/17, 94%). The sum of chromosomal regions being affected by copy-number alterations was significantly higher in methylation cluster 1 compared to cluster 2 (mean 262 vs. 109 Mb, p = 0.001). Of note, loss of chromosome 6 occurred in 9/30 tumors (30%) of methylation cluster 1 and was not observed in cluster 2 tumors (p = 0.01). No relevant methylation differences between sporadic and VHL-related HBs or cystic and non-cystic HBs could be detected. Deconvolution of the bulk DNA methylation profiles revealed four methylation components that were associated with the two methylation clusters suggesting cluster-specific cell-type compositions. In conclusion, methylation profiling of HBs reveals 2 distinct subgroups that mainly associate with anatomical location, cytogenetic profiles and differences in cell type composition, potentially reflecting different cells of origin.

Dataset Information

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

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

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