Micro-Environment Causes Reversible Changes in DNA Methylation and mRNA Expression Profiles in Patient-Derived Glioma Stem Cells
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{"title"=>"Micro-environment causes reversible changes in DNA methylation and mRNA expression profiles in patient-derived glioma stem cells", "type"=>"journal", "authors"=>[{"first_name"=>"Mehmet", "last_name"=>"Baysan", "scopus_author_id"=>"8386447300"}, {"first_name"=>"Kevin", "last_name"=>"Woolard", "scopus_author_id"=>"23096713000"}, {"first_name"=>"Serdar", "last_name"=>"Bozdag", "scopus_author_id"=>"24472576200"}, {"first_name"=>"Gregory", "last_name"=>"Riddick", "scopus_author_id"=>"16432575300"}, {"first_name"=>"Svetlana", "last_name"=>"Kotliarova", "scopus_author_id"=>"6602637499"}, {"first_name"=>"Margaret C.", "last_name"=>"Cam", "scopus_author_id"=>"6701537128"}, {"first_name"=>"Galina I.", "last_name"=>"Belova", "scopus_author_id"=>"9638747900"}, {"first_name"=>"Susie", "last_name"=>"Ahn", "scopus_author_id"=>"7401989985"}, {"first_name"=>"Wei", "last_name"=>"Zhang", "scopus_author_id"=>"57192222152"}, {"first_name"=>"Hua", "last_name"=>"Song", "scopus_author_id"=>"36109020800"}, {"first_name"=>"Jennifer", "last_name"=>"Walling", "scopus_author_id"=>"12807328700"}, {"first_name"=>"Holly", "last_name"=>"Stevenson", "scopus_author_id"=>"7101600410"}, {"first_name"=>"Paul", "last_name"=>"Meltzer", "scopus_author_id"=>"56228323500"}, {"first_name"=>"Howard A.", "last_name"=>"Fine", "scopus_author_id"=>"7006606728"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24728236", "sgr"=>"84899653917", "doi"=>"10.1371/journal.pone.0094045", "scopus"=>"2-s2.0-84899653917", "pui"=>"372981511", "issn"=>"19326203"}, "id"=>"bf7e6810-3389-3817-b722-35bd5eef9fc2", "abstract"=>"In vitro and in vivo models are widely used in cancer research. Characterizing the similarities and differences between a patient's tumor and corresponding in vitro and in vivo models is important for understanding the potential clinical relevance of experimental data generated with these models. Towards this aim, we analyzed the genomic aberrations, DNA methylation and transcriptome profiles of five parental tumors and their matched in vitro isolated glioma stem cell (GSC) lines and xenografts generated from these same GSCs using high-resolution platforms. We observed that the methylation and transcriptome profiles of in vitro GSCs were significantly different from their corresponding xenografts, which were actually more similar to their original parental tumors. This points to the potentially critical role of the brain microenvironment in influencing methylation and transcriptional patterns of GSCs. Consistent with this possibility, ex vivo cultured GSCs isolated from xenografts showed a tendency to return to their initial in vitro states even after a short time in culture, supporting a rapid dynamic adaptation to the in vitro microenvironment. These results show that methylation and transcriptome profiles are highly dependent on the microenvironment and growth in orthotopic sites partially reverse the changes caused by in vitro culturing.", "link"=>"http://www.mendeley.com/research/microenvironment-causes-reversible-changes-dna-methylation-mrna-expression-profiles-patientderived-g-1", "reader_count"=>28, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Master"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Master"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>7, "Agricultural and Biological Sciences"=>13, "Neuroscience"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}}, "reader_count_by_country"=>{"Sweden"=>1, "Ukraine"=>1}, "group_count"=>1}

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/1460968"], "description"=>"<p>(A) HC for matched PT-<i>in vitro</i> pairs for five GSC lines. (B) HC for PT and <i>in vitro-in vivo-ex vivo</i> triplicates for early and late passage 827 samples (C) Median expression values for all samples. (D) HC for PT and <i>in vitro-in vivo-ex vivo</i> triplicates for early and late passage 923 samples.</p>", "links"=>[], "tags"=>["Biochemistry", "dna", "DNA modification", "Nucleic acids", "cell biology", "Molecular cell biology", "Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "Comparative genomics", "epigenomics", "genetics", "Cancer genetics", "gene expression", "genomics", "neurology", "Neurological tumors", "glioma", "oncology", "Cancers and neoplasms", "Tumor physiology", "Basic cancer research", "Model organisms", "Animal models", "Mouse models", "1901", "probe"], "article_id"=>996190, "categories"=>["Biological Sciences"], "users"=>["Mehmet Baysan", "Kevin Woolard", "Serdar Bozdag", "Gregory Riddick", "Svetlana Kotliarova", "Margaret C. Cam", "Galina I. Belova", "Susie Ahn", "Wei Zhang", "Hua Song", "Jennifer Walling", "Holly Stevenson", "Paul Meltzer", "Howard A. Fine"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094045.g004", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Trancriptome_data_for_high_variation_std_dev_gt_1_3_1901_probe_sets_/996190", "title"=>"Trancriptome data for high variation (std. dev. >1.3) 1901 probe sets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 02:48:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460965"], "description"=>"<p>(A) Principle Component Analyses (PCA) of 3847 methylation sites with standard deviation more than 0.35. PT represents patient tumor and in vitro represents the corresponding <i>in vitro</i> GSCs. Matched PT-<i>in vitro</i> pairs are connected with lines. (B) Median methylation values for each sample based on selected 3847 sites.</p>", "links"=>[], "tags"=>["Biochemistry", "dna", "DNA modification", "Nucleic acids", "cell biology", "Molecular cell biology", "Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "Comparative genomics", "epigenomics", "genetics", "Cancer genetics", "gene expression", "genomics", "neurology", "Neurological tumors", "glioma", "oncology", "Cancers and neoplasms", "Tumor physiology", "Basic cancer research", "Model organisms", "Animal models", "Mouse models", "methylation", "profiles", "tumors"], "article_id"=>996187, "categories"=>["Biological Sciences"], "users"=>["Mehmet Baysan", "Kevin Woolard", "Serdar Bozdag", "Gregory Riddick", "Svetlana Kotliarova", "Margaret C. Cam", "Galina I. Belova", "Susie Ahn", "Wei Zhang", "Hua Song", "Jennifer Walling", "Holly Stevenson", "Paul Meltzer", "Howard A. Fine"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094045.g002", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DNA_methylation_profiles_for_patient_tumors_and_in_vitro_GSCs_/996187", "title"=>"DNA methylation profiles for patient tumors and <i>in vitro</i> GSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 02:48:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460964"], "description"=>"<p>(A) Comparison of five matched patient tumors and their corresponding <i>in vitro</i> GSCs. Each line represents a sample. Three or four digit code represents GSC id, PT represents patient tumor and invitro represents <i>in vitro</i> GSC. Blue is amplification, red is deletion, purple is loss of heterozygosity and orange is allelic imbalance. Examples of the many differences between PTs and matched <i>in vitro</i> GSCs are loss on chromosome 13 at GSC-827 and gain on chromosomes 4, 8, 9 and 14 at GSC-1228. (B) Comparison of <i>in vitro</i>-<i>in vivo</i>-<i>ex vivo</i> triplicates for early and late passages of two GSCs.</p>", "links"=>[], "tags"=>["Biochemistry", "dna", "DNA modification", "Nucleic acids", "cell biology", "Molecular cell biology", "Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "Comparative genomics", "epigenomics", "genetics", "Cancer genetics", "gene expression", "genomics", "neurology", "Neurological tumors", "glioma", "oncology", "Cancers and neoplasms", "Tumor physiology", "Basic cancer research", "Model organisms", "Animal models", "Mouse models", "alterations", "tumors", "gsc"], "article_id"=>996186, "categories"=>["Biological Sciences"], "users"=>["Mehmet Baysan", "Kevin Woolard", "Serdar Bozdag", "Gregory Riddick", "Svetlana Kotliarova", "Margaret C. Cam", "Galina I. Belova", "Susie Ahn", "Wei Zhang", "Hua Song", "Jennifer Walling", "Holly Stevenson", "Paul Meltzer", "Howard A. Fine"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094045.g001", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Copy_number_alterations_for_patient_tumors_and_in_vitro_in_vivo_ex_vivo_GSC_samples_/996186", "title"=>"Copy number alterations for patient tumors and <i>in vitro</i>, <i>in vivo</i>, <i>ex vivo</i> GSC samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 02:48:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460966"], "description"=>"<p>(A,B) HC and PCA for PT, <i>in vitro</i>, <i>in vivo</i> and <i>ex vivo</i> samples for early and late passages (ep, lp). 6825 sites with standard deviation greater than 0.15 are presented. These sites are not differentially methylated between 827 and 923 (Mann-Whitney p-value more than 0.5). (C) Median methylation values for each sample based on selected 6825 sites.</p>", "links"=>[], "tags"=>["Biochemistry", "dna", "DNA modification", "Nucleic acids", "cell biology", "Molecular cell biology", "Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "Comparative genomics", "epigenomics", "genetics", "Cancer genetics", "gene expression", "genomics", "neurology", "Neurological tumors", "glioma", "oncology", "Cancers and neoplasms", "Tumor physiology", "Basic cancer research", "Model organisms", "Animal models", "Mouse models", "methylation", "profiles", "tumors", "gscs"], "article_id"=>996188, "categories"=>["Biological Sciences"], "users"=>["Mehmet Baysan", "Kevin Woolard", "Serdar Bozdag", "Gregory Riddick", "Svetlana Kotliarova", "Margaret C. Cam", "Galina I. Belova", "Susie Ahn", "Wei Zhang", "Hua Song", "Jennifer Walling", "Holly Stevenson", "Paul Meltzer", "Howard A. Fine"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094045.g003", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DNA_methylation_profiles_of_patient_tumors_and_in_vitro_in_vivo_ex_vivo_GSCs_for_two_cell_lines_/996188", "title"=>"DNA methylation profiles of patient tumors and <i>in vitro</i>, <i>in vivo</i>, <i>ex vivo</i> GSCs for two cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 02:48:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460969"], "description"=>"<p>Differentially expressed genes determined with paired t-test. Genes with false discovery rate less than 0.05 (Benjamini-Hochberg) and absolute fold change greater than three are used. Differentially methylated sites determined with paired non-parametric Quade test and sites with false discovery rate less than 0.05 (Benjamini-Hochberg) and absolute methylation difference greater than 0.3 are used.</p>", "links"=>[], "tags"=>["Biochemistry", "dna", "DNA modification", "Nucleic acids", "cell biology", "Molecular cell biology", "Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "Comparative genomics", "epigenomics", "genetics", "Cancer genetics", "gene expression", "genomics", "neurology", "Neurological tumors", "glioma", "oncology", "Cancers and neoplasms", "Tumor physiology", "Basic cancer research", "Model organisms", "Animal models", "Mouse models", "methylation", "differences", "paired", "pairs", "differentially", "methylated"], "article_id"=>996191, "categories"=>["Biological Sciences"], "users"=>["Mehmet Baysan", "Kevin Woolard", "Serdar Bozdag", "Gregory Riddick", "Svetlana Kotliarova", "Margaret C. Cam", "Galina I. Belova", "Susie Ahn", "Wei Zhang", "Hua Song", "Jennifer Walling", "Holly Stevenson", "Paul Meltzer", "Howard A. Fine"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094045.g005", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fold_changes_x_axis_and_mean_methylation_differences_y_axis_between_paired_in_vitro_PT_pairs_for_both_differentially_expressed_and_differentially_methylated_genes_/996191", "title"=>"Fold changes (x-axis) and mean methylation differences (y-axis) between paired <i>in vitro</i>-PT pairs for both differentially expressed and differentially methylated genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 02:48:52"}

PMC Usage Stats | Further Information

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Relative Metric

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