Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MCAM_glioma_stem_cells

ABSTRACT: To examine methylation profile of the CpG promoters in glioma stem cells

ORGANISM(S): Homo sapiens

DISEASE(S): normal

SUBMITTER: Atsushi Natsume

PROVIDER: E-TABM-1122 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Chromatin regulator PRC2 is a key regulator of epigenetic plasticity in glioblastoma.

Natsume Atsushi A Ito Motokazu M Katsushima Keisuke K Ohka Fumiharu F Hatanaka Akira A Shinjo Keiko K Sato Shinya S Takahashi Satoru S Ishikawa Yuta Y Takeuchi Ichiro I Shimogawa Hiroki H Uesugi Motonari M Okano Hideyuki H Kim Seung U SU Wakabayashi Toshihiko T Issa Jean-Pierre J JP Sekido Yoshitaka Y Kondo Yutaka Y

Cancer research 20130529 14

Tumor cell plasticity contributes to functional and morphologic heterogeneity. To uncover the underlying mechanisms of this plasticity, we examined glioma stem-like cells (GSC) where we found that the biologic interconversion between GSCs and differentiated non-GSCs is functionally plastic and accompanied by gain or loss of polycomb repressive complex 2 (PRC2), a complex that modifies chromatin structure. PRC2 mediates lysine 27 trimethylation on histone H3 and in GSC it affected pluripotency or ...[more]

PMID: 23720055

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Project description:A large-scale characterization of the methylation states of candidate CpG islands (CGIs) throughout the gastric cancer methylome has not previously been conducted. Genome-wide DNA methylation profiles were compared between 4 metastatic and 4 non-metastatic gastric carcinomas (GCs) and their surgical margins (SMs). The GC genome showed significantly higher proportions of hypomethylation in the promoter and exon-1 regions, as well as increased hypermethylation of intragenic fragments when compared to SMs. Differential methylation was observed in CGIs near transcription start sites of 546 genes between GCs and SMs, and 601 genes between metastatic and non-metastatic GCs. From the list of differentially methylated CGIs, 68 candidate genes and 10 known tumor-related genes were selected for further characterization based on their known molecular function using DHPLC. Significant differential methylation was validated in the CGIs of 15 genes between GCs and SMs (Ps<0.05) and confirmed using bisulfite-sequencing. These genes include BMP3, BNIP3, CDKN2A, ECEL1, ELK1, GFRA1, HOXD10, KCNH1, PSMD10, PTPRT, SIGIRR, SRF, TBX5, TFPI2, and ZNF382. Hypomethylation of CGIs correlated with up-regulation of GFRA1 expression in GCs, while hypermethylation of other genes inactivated their transcription. Most importantly, prevalence of GFRA1, SRF, and ZNF382 methylation alterations were inversely and coordinately associated with GC metastasis and the patients’ overall survival throughout discovery and testing cohorts in China as well as independent validation cohorts in Japan and Korea. In conclusion, methylation changes in the CGIs of 15 genes correlated strongly with GC development. GFRA1 hypomethylation and SRF and ZNF382 hypermethylation are potential synergistic biomarkers for the prediction of GC metastasis. To identify differential methylation of CGIs related to GC development and metastasis, genome-wide DNA methylation changes in 8 pairs of GC and SM samples were analysed using the MCAM assay with a 99K custom-designed Agilent oligonucleotide microarray composed of 99,027 probes targeting 6,177 unique protein-coding genes containing at least two methylation-sensitive/insensitive SmaI/ XmaI restriction sites (CCC|GGG/ C|CmCGGG) as described in Shen et al, PLoS Genet 3, 2023-2036 (2007).

Project description:Friable embryogenic callus (FEC) has been considered as the most suitable materials for efficient genetic transformation of cassava. Due to heavy genotype dependence on FEC induction and being amenable to somaclonal variation, the production and maintaining of reliable FEC is a limitation factor for cassava genetic transformation. Identification of key elements involving in biological processes from somatic embryos (SEs) to the FEC at different stages will provide critical insights for FEC improvement. Cytological observation showed the dramatic change of subcellular structures among SEs, fresh FEC (FFEC) and old FEC (OFEC). Decrease of sucrose and increase of fructose and glucose were detected in OFEC. A total of 6871 differentially expressed genes (DEGs) were identified from SEs, FFEC and OFEC by RNA-seq. Analysis of the DEGs showed that FEC induction was accompanied by the process of dedifferentiation, whereas the epigenetics modification occurred during the continuous subculturing process. The cell structure was reconstructed, mainly including the GO terms of "cell periphery" and "external encapsulating structure"; in parallel, the internal mechanisms were changed correspondingly, including the metabolisms of process (glycolysis) and compounds(alanine, aspartate, and glutamate). The significant reduction of genomic DNA methylation in OFEC indicates altered gene expression via chromatin modification. These results indicate that the induction and long-term subculture of FEC is a complicated biological process involving changes of genome modification, gene expression and subcellular reconstruction. The findings will be useful for improving FEC induction and maintenance from farmer-preferred cassava cultivars that are recalcitrant to genetic transformation, hence improving cassava through genetic engineering. Two-week-old SEs cultured on GD, FFEC emerging from SEs, and 9-month-old OFEC were used for analysis. Each sample was mixtured from six indepedent replicates and were collected for RNA extraction respectively.

Dataset Information

MCAM_glioma_stem_cells

Publications

Chromatin regulator PRC2 is a key regulator of epigenetic plasticity in glioblastoma.

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