scholarly journals Micro-Environment Causes Reversible Changes in DNA Methylation and mRNA Expression Profiles in Patient-Derived Glioma Stem Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e94045 ◽  
Author(s):  
Mehmet Baysan ◽  
Kevin Woolard ◽  
Serdar Bozdag ◽  
Gregory Riddick ◽  
Svetlana Kotliarova ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Glioma Stem Cells

scholarly journals Accumulation of DNA methylation alterations in paediatric glioma stem cells following fractionated dose irradiation

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Anna Danielsson ◽  
Kristell Barreau ◽  
Teresia Kling ◽  
Magnus Tisell ◽  
Helena Carén
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Cellular Response ◽  
Glioma Stem Cells ◽  
Proliferation And Differentiation ◽  
Radiation Resistant ◽  
Radiation Induced ◽  
Induced Changes ◽  
Regulatory Functions

Abstract Background Radiation is an important therapeutic tool. However, radiotherapy has the potential to promote co-evolution of genetic and epigenetic changes that can drive tumour heterogeneity, formation of radioresistant cells and tumour relapse. There is a clinical need for a better understanding of DNA methylation alterations that may follow radiotherapy to be able to prevent the development of radiation-resistant cells. Methods We examined radiation-induced changes in DNA methylation profiles of paediatric glioma stem cells (GSCs) in vitro. Five GSC cultures were irradiated in vitro with repeated doses of 2 or 4 Gy. Radiation was given in 3 or 15 fractions. DNA methylation profiling using Illumina DNA methylation arrays was performed at 14 days post-radiation. The cellular characteristics were studied in parallel. Results Few fractions of radiation did not result in significant accumulation of DNA methylation alterations. However, extended dose fractionations changed DNA methylation profiles and induced thousands of differentially methylated positions, specifically in enhancer regions, sites involved in alternative splicing and in repetitive regions. Radiation induced dose-dependent morphological and proliferative alterations of the cells as a consequence of the radiation exposure. Conclusions DNA methylation alterations of sites with regulatory functions in proliferation and differentiation were identified, which may reflect cellular response to radiation stress through epigenetic reprogramming and differentiation cues.

scholarly journals Development and Validation of a Prognostic Nomogram Based on DNA Methylation-Driven Genes for Patients With Ovarian Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Zhou ◽  
Shasha Hong ◽  
Bingshu Li ◽  
Cheng Liu ◽  
Ming Hu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Risk Score ◽  
Cox Regression ◽  
Expression Profiles ◽  
Figo Stage ◽  
Prognostic Indicator ◽  
Tissue Expression ◽  
The Cancer Genome Atlas

Background: DNA methylation affects the development, progression, and prognosis of various cancers. This study aimed to identify DNA methylated-differentially expressed genes (DEGs) and develop a methylation-driven gene model to evaluate the prognosis of ovarian cancer (OC).Methods: DNA methylation and mRNA expression profiles of OC patients were downloaded from The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases. We used the R package MethylMix to identify DNA methylation-regulated DEGs and built a prognostic signature using LASSO Cox regression. A quantitative nomogram was then drawn based on the risk score and clinicopathological features.Results: We identified 56 methylation-related DEGs and constructed a prognostic risk signature with four genes according to the LASSO Cox regression algorithm. A higher risk score not only predicted poor prognosis, but also was an independent poor prognostic indicator, which was validated by receiver operating characteristic (ROC) curves and the validation cohort. A nomogram consisting of the risk score, age, FIGO stage, and tumor status was generated to predict 3- and 5-year overall survival (OS) in the training cohort. The joint survival analysis of DNA methylation and mRNA expression demonstrated that the two genes may serve as independent prognostic biomarkers for OS in OC.Conclusion: The established qualitative risk score model was found to be robust for evaluating individualized prognosis of OC and in guiding therapy.

scholarly journals A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Zuhua Chen ◽  
Bo Liu ◽  
Minxiao Yi ◽  
Hong Qiu ◽  
Xianglin Yuan
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Risk Model ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Dna Hypomethylation

PurposeThe exploration and interpretation of DNA methylation-driven genes might contribute to molecular classification, prognostic prediction and therapeutic choice. In this study, we built a prognostic risk model via integrating analysis of the transcriptome and methylation profile for patients with gastric cancer (GC).MethodsThe mRNA expression profiles, DNA methylation profiles and corresponding clinicopathological information of 415 GC patients were downloaded from The Cancer Genome Atlas (TCGA). Differential expression and correlation analysis were performed to identify DNA methylation-driven genes. The candidate genes were selected by univariate Cox regression analyses followed by the least absolute shrinkage and selection operator (LASSO) regression. A prognostic risk nomogram model was then built together with clinicopathological parameters.Results5 DNA methylation-driven genes (CXCL3, F5, GNAI1, GAMT and GHR) were identified by integrated analyses and selected to construct the prognostic risk model with clinicopathological parameters. High expression and low DNA hypermethylation of F5, GNAI1, GAMT and GHR, as well as low expression and high DNA hypomethylation of CXCL3 were significantly associated with poor prognosis rates, respectively. The high-risk group showed a significantly shorter prognosis than the low-risk group in the TCGA dataset (HR = 0.212, 95% CI = 0.139–0.322, P = 2e-15). The final nomogram model showed high predictive efficiency and consistency in the training and validation group.ConclusionWe construct and validate a prognostic nomogram model for GC based on five DNA methylation-driven genes with high performance and stability. This nomogram model might be a powerful tool for prognosis evaluation in the clinic and also provided novel insights into the epigenetics in GC.

Identifying MicroRNA and mRNA Expression Profiles in Embryonic Stem Cells Derived from Parthenogenetic, Androgenetic and Fertilized Blastocysts

2013 ◽  
Vol 40 (4) ◽  
pp. 189-200 ◽  
Author(s):  
Xiang-Shun Cui ◽  
Xing-Hui Shen ◽  
Shao-Chen Sun ◽  
Sun-Wha Cho ◽  
Young-Tae Heo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Embryonic Stem

scholarly journals CB-02 * MiRNA EXPRESSION PROFILES OF GLIOMA STEM CELLS AND THEIR ASSOCIATION WITH THE MESENCHYMAL TRANSFORMATION OF THESE CELLS

2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v41-v41
Author(s):  
A. Bier ◽  
S. Finniss ◽  
S. Cazacu ◽  
C. Xiang ◽  
H. K. Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Glioma Stem Cells ◽  
Mirna Expression Profiles ◽  
Mesenchymal Transformation

scholarly journals Integrated analysis of DNA methylome and transcriptome reveals the differences in biological characteristics of porcine mesenchymal stem cells from bone marrow and umbilical cord

2019 ◽  
Author(s):  
Yalan Yang ◽  
Zhiguo Liu ◽  
Weimin Zhao ◽  
Lei Huang ◽  
Tianwen Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Expression Profiles ◽  
Biological Characteristics ◽  
Integrated Analysis ◽  
Differentiation Potential

Abstract Background Bone marrow (BM) and umbilical cord (UC) are the main sources of mesenchymal stem cells (MSCs). These two MSCs display significant differences in many biological characteristics, yet the underlying molecular mechanisms need to be explored. Results In this study, to better understanding the biological features of MSCs, we isolated BMMSCs and UCMSCs from inbred Wuzhishan miniature pigs and generated the first global DNA methylation and gene expression profiles of porcine MSCs. The results showed that the osteogenic and adipogenic differentiation ability of porcine BMMSCs is stronger than that of UCMSCs. Stem cell surface marker CD90 were positively detected in both BMMSCs and UCMSCs. 587 genes were differentially methylated (280 hypermethylated and 307 hypomethylated) at the promoter regions between BMMSCs and UCMSCs. Meanwhile, 1,979 differentially expressed genes (1,407 up-regulated and 572 down-regulated) were identified between BMMSCs and UCMSCs. Integrative analysis reveals that 120 genes displayed differences in both gene expression and promoter methylation. Gene Ontology enrichment analysis revealed that these differential genes were associated with cell differentiation, cell migration, and immunogenicity properties. Remarkably, skeletal system development related genes were significantly hypomethylated and up-regulated in UCMSCs, while cell cycle genes were significantly higher down-regulated and hypermethylated, implying UCMSCs have higher cell proliferative activity and lower osteogenic differentiation potential than BMMSCs. Conclusions Our results indicate that DNA methylation plays an important role in regulating the biological characteristics differences between BMMSCs and UCMSCs. The study might provide a molecular theory basis for the application of porcine MSCs in human.

scholarly journals Effects of Interleukin-1β on Long Noncoding RNA and mRNA Expression Profiles of Human Synovial Fluid-derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Yang-peng Sun ◽  
Yun-yang Lu ◽  
Jianyu Chen ◽  
Jia-hao Bao ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Synovial Fluid ◽  
Mrna Expression ◽  
Temporomandibular Joint ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Biological Behavior ◽  
Antisense Lncrnas

Abstract Synovial fluid-derived mesenchymal stem cells (SFMSCs) play important regulatory roles in the physiological balance of the temporomandibular joint. Interleukin (IL)-1β regulates the biological behavior of SFMSCs; however, the effects of IL-1β on long noncoding RNA (lncRNA) and mRNA expression in SFMSCs in the temporomandibular joint are unclear. Here, we evaluated the lncRNA and mRNA expression profiles of IL-1β-stimulated SFMSCs. Using microarrays, we identified 286 lncRNAs (222 upregulated, 64 downregulated) and 304 mRNAs (242 upregulated, 62 downregulated) that were differentially expressed after treatment with IL-1β (fold change ≥ 2, P < 0.05). Kyoto Encyclopedia of Genes and Genomes pathway analysis found that one of the most significantly enriched pathways was the NF-κB pathway. Five paired antisense lncRNAs and mRNAs, eight paired enhancer lncRNAs and mRNAs, and nine paired long intergenic noncoding RNAs and mRNAs were predicted to be co-expressed. A network constructed by the top 30 k-score genes was visualized and evaluated. We found a co-expression relationship between ENST00000427824 and ENST00000307407 and between LOC541472 and IL6, which are related to NF-κB pathway activation. Overall, our results provide important insights into changes in lncRNA and mRNA expression in IL-1β-stimulated SFMSCs, which can facilitate the identification of potential therapeutic targets.

scholarly journals DNA methylation and mRNA expression profiles in bovine oocytes derived from prepubertal and adult donors

Reproduction ◽  
2012 ◽  
Vol 144 (3) ◽  
pp. 319-330 ◽  
Author(s):  
Mike Diederich ◽  
Tamara Hansmann ◽  
Julia Heinzmann ◽  
Brigitte Barg-Kues ◽  
Doris Herrmann ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Bos Taurus ◽  
Expression Profiles ◽  
Methylation Status ◽  
Transcript Abundance ◽  
Developmental Competence ◽  
Satellite Sequences ◽  
Bovine Oocytes

The developmental capacity of oocytes from prepubertal cattle is reduced compared with their adult counterparts, and epigenetic mechanisms are thought to be involved herein. Here, we analyzed DNA methylation in three developmentally important, nonimprinted genes (SLC2A1, PRDX1, ZAR1) and two satellite sequences, i.e. ‘bovine testis satellite I’ (BTS) and ‘Bos taurus alpha satellite I’ (BTαS). In parallel, mRNA expression of the genes was determined by quantitative real-time PCR. Oocytes were retrieved from prepubertal calves and adult cows twice per week over a 3-week period by ultrasound-guided follicular aspiration after treatment with FSH and/or IGF1. Both immature and in vitro matured prepubertal and adult oocytes showed a distinct hypomethylation profile of the three genes without differences between the two types of donors. The methylation status of the BTS sequence changed according to the age and treatment while the methylation status of BTαS sequence remained largely unchanged across the different age and treatment groups. Relative transcript abundance of the selected genes was significantly different in immature and in vitro matured oocytes; only minor changes related to origin and treatment were observed. In conclusion, methylation levels of the investigated satellite sequences were high (>50%) in all groups and showed significant variation depending on the age, treatment, or in vitro maturation. To what extent this is involved in the acquisition of developmental competence of bovine oocytes needs further study.

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