scholarly journals DNA methylation status correlates with adult β-cell regeneration capacity

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ishant Khurana ◽  
Keith Al-Hasani ◽  
Scott Maxwell ◽  
Harikrishnan K.N. ◽  
Jun Okabe ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Status ◽  
Cell Reprogramming ◽  
Cell Regeneration ◽  
Regeneration Capacity ◽  
Β Cell ◽  
Major Significance

AbstractThe role of DNA methylation in β-cell neogenesis is poorly understood. We report that during the process of induced cell reprogramming, methylation content of the Ngn3 and Sox11 genes are diminished. These findings emphasise DNA methylation is a barrier in β-cell regeneration in adulthood, a well described pathophysiological phenomenon of major significance in explaining β-cell deficiency in diabetes in the adult pancreas.

scholarly journals Title Page Title: The role of DNA methylation in the accumulation of iridoid glycosides in Rehmannia glutinosa

2021 ◽  
Author(s):  
Tianyu Dong ◽  
Xiaoyan Wei ◽  
Qianting Qi ◽  
Peilei Chen ◽  
Yanqing Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Secondary Metabolites ◽  
Iridoid Glycosides ◽  
Methylation Status ◽  
Plant Secondary Metabolites ◽  
Dna Demethylation ◽  
Terpene Biosynthesis ◽  
The Relationship

Abstract Background: Epigenetic regulation plays a significant role in the accumulation of plant secondary metabolites. The terpenoids are the most abundant in the secondary metabolites of plants, iridoid glycosides belong to monoterpenoids which is one of the main medicinal components of R.glutinosa. At present, study on iridoid glycosides mainly focuses on its pharmacology, accumulation and distribution, while the mechanism of its biosynthesis and the relationship between DNA methylation and plant terpene biosynthesis are seldom reports. Results: The research showed that the expression of DXS, DXR, 10HGO, G10H, GPPS and accumulation of iridoid glycosides increased at first and then decreased with the maturity of R.glutinosa, and under different concentrations of 5-azaC, the expression of DXS, DXR, 10HGO, G10H, GPPS and the accumulation of total iridoid glycosides were promoted, the promotion effect of low concentration (15μM-50μM) was more significant, the content of genomic DNA 5mC decreased significantly, the DNA methylation status of R.glutinosa genomes was also changed. DNA demethylation promoted gene expression and increased the accumulation of iridoid glycosides, but excessive demethylation inhibited gene expression and decreased the accumulation of iridoid glycosides. Conclusion: The analysis of DNA methylation, gene expression, and accumulation of iridoid glycoside provides insights into accumulation of terpenoids in R.glutinosa and lays a foundation for future studies on the effects of epigenetics on the synthesis of secondary metabolites.

A role of age-dependent DNA methylation reprogramming in regulating the regeneration capacity of Boea hygrometrica leaves

2019 ◽  
Vol 20 (1) ◽  
pp. 133-149 ◽  
Author(s):  
Run-Ze Sun ◽  
En-Hui Zuo ◽  
Jin-Feng Qi ◽  
Yang Liu ◽  
Chih-Ta Lin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Regeneration Capacity ◽  
Age Dependent ◽  
Boea Hygrometrica

scholarly journals Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ka-Cheuk Liu ◽  
Alethia Villasenor ◽  
Maria Bertuzzi ◽  
Nicole Schmitner ◽  
Niki Radros ◽  
...  
Keyword(s):  
Calcium Influx ◽  
Lineage Tracing ◽  
Cell Regeneration ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Alternative Source ◽  
Cell Ablation ◽  
Mesodermal Origin

To investigate the role of the vasculature in pancreatic β-cell regeneration, we crossed a zebrafish β-cell ablation model into the avascular npas4l mutant (i.e. cloche). Surprisingly, β-cell regeneration increased markedly in npas4l mutants owing to the ectopic differentiation of β-cells in the mesenchyme, a phenotype not previously reported in any models. The ectopic β-cells expressed endocrine markers of pancreatic β-cells, and also responded to glucose with increased calcium influx. Through lineage tracing, we determined that the vast majority of these ectopic β-cells has a mesodermal origin. Notably, ectopic β-cells were found in npas4l mutants as well as following knockdown of the endothelial/myeloid determinant Etsrp. Together, these data indicate that under the perturbation of endothelial/myeloid specification, mesodermal cells possess a remarkable plasticity enabling them to form β-cells, which are normally endodermal in origin. Understanding the restriction of this differentiation plasticity will help exploit an alternative source for β-cell regeneration.

scholarly journals Regenerating insulin-producing β-cells ectopically from a mesodermal origin in the absence of endothelial specification

2021 ◽  
Author(s):  
Ka-Cheuk Liu ◽  
Alethia Villasenor ◽  
Nicole Schmitner ◽  
Niki Radros ◽  
Linn Rautio ◽  
...  
Keyword(s):  
Lineage Tracing ◽  
Cell Regeneration ◽  
Β Cells ◽  
Β Cell ◽  
Alternative Source ◽  
Glucose Levels ◽  
Cell Ablation ◽  
Mesodermal Origin ◽  
Ablation Model

AbstractTo investigate the role of the vasculature in pancreatic β-cell regeneration, we crossed a zebrafish β-cell ablation model into the avascular npas4l mutant (i.e. cloche). Surprisingly, β-cell regeneration increased markedly in npas4l mutants owing to the ectopic differentiation of β-cells in the mesenchyme, a phenotype not previously reported in any models. The ectopic β-cells expressed endocrine markers of pancreatic β-cells, and also reduced glucose levels in the β-cell ablation model. Through lineage tracing, we determined that the vast majority of these ectopic β-cells derived from the mesodermal lineage. Notably, ectopic β-cells were found in npas4l mutants as well as following knockdown of the endothelial determinant Etv2. Together, these data indicate that in the absence of endothelial specification, mesodermal cells possess a remarkable plasticity enabling them to form β-cells, which are normally endodermal in origin. Understanding the restriction of this differentiation plasticity will help exploit an alternative source for β-cell regeneration.

scholarly journals DNA Methylation and Gene Expression Profiling of Ewing Sarcoma Primary Tumors Reveal Genes That Are Potential Targets of Epigenetic Inactivation

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Nikul Patel ◽  
Jennifer Black ◽  
Xi Chen ◽  
A. Mario Marcondes ◽  
William M. Grady ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Lines ◽  
Ewing Sarcoma ◽  
Methylation Status ◽  
Primary Cultures ◽  
Human Mesenchymal Stem Cell ◽  
Primary Tumors ◽  
Hypermethylated Genes

The role of aberrant DNA methylation in Ewing sarcoma is not completely understood. The methylation status of 503 genes in 52 formalin-fixed paraffin-embedded EWS tumors and 3 EWS cell lines was compared to human mesenchymal stem cell primary cultures (hMSCs) using bead chip methylation analysis. Relative expression of methylated genes was assessed in 5-Aza-2-deoxycytidine-(5-AZA)-treated EWS cell lines and in a cohort of primary EWS samples and hMSCs by gene expression and quantitative RT-PCR. 129 genes demonstrated statistically significant hypermethylation in EWS tumors compared to hMSCs. Thirty-six genes were profoundly methylated in EWS and unmethylated in hMSCs. 5-AZA treatment of EWS cell lines resulted in upregulation of expression of hundreds of genes including 162 that were increased by at least 2-fold. The expression of 19 of 36 candidate hypermethylated genes was increased following 5-AZA. Analysis of gene expression from an independent cohort of tumors confirmed decreased expression of six of nineteen hypermethylated genes (AXL, COL1A1, CYP1B1, LYN, SERPINE1,) andVCAN. Comparing gene expression and DNA methylation analyses proved to be an effective way to identify genes epigenetically regulated in EWS. Further investigation is ongoing to elucidate the role of these epigenetic alterations in EWS pathogenesis.

scholarly journals Genetic and Epigenetic Alterations Induced by Pesticide Exposure: Integrated Analysis of Gene Expression, microRNA Expression and DNA Methylation Datasets

2021 ◽  
Vol 18 (16) ◽  
pp. 8697
Author(s):  
Federica Giambò ◽  
Gian Leone ◽  
Giuseppe Gattuso ◽  
Roberta Rizzo ◽  
Alessia Cosentino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Pesticide Exposure ◽  
Methylation Status ◽  
Microrna Expression ◽  
Integrated Analysis ◽  
Epigenetic Alterations ◽  
Expression Levels ◽  
Prediction Tools

Environmental or occupational exposure to pesticides is considered one of the main risk factors for the development of various diseases. Behind the development of pesticide-associated pathologies, there are both genetic and epigenetic alterations, where these latter are mainly represented by the alteration in the expression levels of microRNAs and by the change in the methylation status of the DNA. At present, no studies have comprehensively evaluated the genetic and epigenetic alterations induced by pesticides; therefore, the aim of the present study was to identify modifications in gene miRNA expression and DNA methylation useful for the prediction of pesticide exposure. For this purpose, an integrated analysis of gene expression, microRNA expression, and DNA methylation datasets obtained from the GEO DataSets database was performed to identify putative genes, microRNAs, and DNA methylation hotspots associated with pesticide exposure and responsible for the development of different diseases. In addition, DIANA-miRPath, STRING, and GO Panther prediction tools were used to establish the functional role of the putative biomarkers identified. The results obtained demonstrated that pesticides can modulate the expression levels of different genes and induce different epigenetic alterations in the expression levels of miRNAs and in the modulation of DNA methylation status.

scholarly journals Gene-associated methylation status of ST14 as a predictor of survival and hormone receptor positivity in breast Cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang-Hong Dai ◽  
Ying-Fu Wang ◽  
Po-Chien Shen ◽  
Cheng-Hsiang Lo ◽  
Jen-Fu Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Prognostic Value ◽  
Potential Role ◽  
Cox Model ◽  
Methylation Status ◽  
Specific Gene ◽  
Molecular Features ◽  
Gene Sets

Abstract Background Genomic profiles of specific gene sets have been established to guide personalized treatment and prognosis for patients with breast cancer (BC). However, epigenomic information has not yet been applied in a clinical setting. ST14 encodes matriptase, a proteinase that is widely expressed in BC with reported prognostic value. Methods In this present study, we evaluated the effect of ST14 DNA methylation (DNAm) on overall survival (OS) of patients with BC as a representative example to promote the use of the epigenome in clinical decisions. We analyzed publicly available genomic and epigenomic data from 1361 BC patients. Methylation was characterized by the β-value from CpG probes based on sequencing with the Illumina Human 450 K platform. Results A high mean DNAm (β > 0.6779) across 34 CpG probes for ST14, as the gene-associated methylation (GAM) pattern, was associated with a longer OS after adjusting age, stage, histology and molecular features in Cox model (p value < 0.001). A high GAM status was also associated with a higher XBP1 expression level and higher proportion of hormone-positive BC (p value < 0.001). Pathway analysis revealed that altered GAM was related to matrisome-associated pathway. Conclusions Here we show the potential role of ST14 DNAm in BC prognosis and warrant further study.

scholarly journals The Methylation Status of the Epigenome: Its Emerging Role in the Regulation of Tumor Angiogenesis and Tumor Growth, and Potential for Drug Targeting

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 268 ◽  
Author(s):  
Luciano Pirola ◽  
Oskar Ciesielski ◽  
Aneta Balcerczyk
Keyword(s):  
Dna Methylation ◽  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Methylation Status ◽  
Angiogenesis Inhibitors ◽  
Post Translational Modifications ◽  
Methylation Patterns ◽  
Cancerous Cells ◽  
Transcriptional State

Approximately 50 years ago, Judah Folkman raised the concept of inhibiting tumor angiogenesis for treating solid tumors. The development of anti-angiogenic drugs would decrease or even arrest tumor growth by restricting the delivery of oxygen and nutrient supplies, while at the same time display minimal toxic side effects to healthy tissues. Bevacizumab (Avastin)—a humanized monoclonal anti VEGF-A antibody—is now used as anti-angiogenic drug in several forms of cancers, yet with variable results. Recent years brought significant progresses in our understanding of the role of chromatin remodeling and epigenetic mechanisms in the regulation of angiogenesis and tumorigenesis. Many inhibitors of DNA methylation as well as of histone methylation, have been successfully tested in preclinical studies and some are currently undergoing evaluation in phase I, II or III clinical trials, either as cytostatic molecules—reducing the proliferation of cancerous cells—or as tumor angiogenesis inhibitors. In this review, we will focus on the methylation status of the vascular epigenome, based on the genomic DNA methylation patterns with DNA methylation being mainly transcriptionally repressive, and lysine/arginine histone post-translational modifications which either promote or repress the chromatin transcriptional state. Finally, we discuss the potential use of “epidrugs” in efficient control of tumor growth and tumor angiogenesis.

scholarly journals DNA Methylation in Osteoarthritis: Current Status and Therapeutic Implications

2018 ◽  
Vol 12 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Antonio Miranda-Duarte
Keyword(s):  
Dna Methylation ◽  
Genetic Factors ◽  
Methylation Status ◽  
Gene Repression ◽  
Current Status ◽  
Multifactorial Disease ◽  
Review Of The Literature ◽  
Therapeutic Implications ◽  
Genome Wide

Background: Primary Osteoarthritis (OA) is a multifactorial disease in which genetic factors are strongly associated with its development; however, recently it has been observed that epigenetic modifications are also involved in the pathogenesis of OA. DNA methylation is related to gene silencing, and several studies have investigated its role in the loci of different pathways or molecules associated to OA. Objective: This review is focused on the current status of DNA methylation studies related to OA pathogenesis. Method: A review of the literature was conducted on searching in PUBMED for original papers on DNA methylation in OA. Conclusion: The DNA methylation research of loci related to OA pathogenesis has shown a correlation between methylation and gene repression; however, there are some exceptions to this rule. Recently, the development of genome-wide methylation and genome-wide hydroxymethylation profiles has demonstrated that several genes previously associated with OA can have changes in their methylation status, favoring the development of the disease, and these have even shown the role of other epigenetic markers.

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