Analysis of cervical carcinomas and cervical cell lines privides insight into gene expression profiling in mexican women
Krüppel Like Factors Family Expression in Cervical Cancer Cells.
Specimen part, Cell line
View SamplesPurpose: DNA methyltransferase 3A (DNMT3A) mediates de novo DNA methylation. Mutations in DNMT3A are associated with hematological malignancies, most frequently acute myeloid leukemia. DNMT3A mutations are hypothesized to establish a pre-leukemic state, rendering cells vulnerable to secondary oncogenic mutations and malignant transformation. However, the mechanisms by which DNMT3A mutations contribute to leukemogenesis are not well-defined. Methods: mRNA profiles of wild-type (WT) and DNMT3A mutated k562 cell lines were generated by deep sequencing, using Illumina HiSeq2500. Sequence reads were trimmed to remove possible adapter sequences and nucleotides with poor quality at the ends. Remaining sequence reads were then aligned to the human reference genome (hg19) using Tophat2. Gene read counts were measured using FeatureCounts and FPKM values were calculated with cufflinks. edgeR was used to identify differentially expressed genes between conditions, and topGO was used for annotation (Alexa, Rahnenfuhrer, and Lengauer, 2006). Sample comparison for differential gene expression was as follows: WTblk and WT1 versus MT2, MT3, MT4, and MT5. Gene enrichment set analysis (GSEA) was conducted with KEGG, Biocarta, and Reactome pathway datasets (Subramanian et al., 2005). Results: DNMT3A-mutated cells displayed impaired differentiation capacity. RNA-seq was used to compare transcriptomes of DNMT3A-mutated and WT cells; DNMT3A ablation resulted in downregulation of genes involved in spliceosome function, causing dysfunction of RNA splicing. Unexpectedly, we observed DNMT3A-mutated cells to exhibit marked genomic instability and an impaired DNA damage response compared to WT. Conclusions: CRISPR/Cas9-mediated DNMT3A-mutated K562 cells may be used to model effects of DNMT3A mutations in human cells. Our findings implicate aberrant splicing and induction of genomic instability as potential mechanisms by which DNMT3A mutations might predispose to malignancy. Overall design: mRNA profiles of wild type (WT) and DNMT3A mutated K562 cell lines were generated by deep sequencing using Illumina HiSeq2500
Abnormal RNA splicing and genomic instability after induction of DNMT3A mutations by CRISPR/Cas9 gene editing.
Specimen part, Cell line, Subject
View SamplesPrevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, in addition, the mechanisms underlying sublingual immunotherapy (SLIT) are still unknown.
Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics.
Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DNMT1-interacting RNAs block gene-specific DNA methylation.
Cell line, Treatment
View SamplesWe used the microarray analysis to detail the gene expression profile from the leukemic cell line HL-60
DNMT1-interacting RNAs block gene-specific DNA methylation.
Cell line
View SamplesIdentification of the all RNA species associated with DNMT1. Using a comparative genome-scale approach we identified and correlated the RNA species physically associated with DNMT1 and proximal to the annotated genes to the methylation status of the corresponding loci and expression levels of the respective genes. This comparative approach delineated the first -DNMT1 centered- 'epitranscriptome' map, a comprehensive map cross-referencing DNMT1-interacting transcripts to (i) DNA methylation and (ii) gene expression profile. Overall design: Relationship between DNMT1-RNA interactions, DNA methylation and gene expression
DNMT1-interacting RNAs block gene-specific DNA methylation.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Autophagy maintains the metabolism and function of young and old stem cells.
Specimen part
View SamplesAutophagy is critical for protecting HSCs from metabolic stress. Here, we used a genetic approach to inactivate autophagy in adult HSCs by deleting the Atg12 gene. We show that loss of autophagy causes accumulation of mitochondria and an oxidative phosphorylation (OXPHOS)-activated metabolic state, which drives accelerated myeloid differentiation likely through epigenetic deregulations rather than transcriptional changes, and impairs HSC self-renewal activity and regenerative potential.
Autophagy maintains the metabolism and function of young and old stem cells.
Specimen part
View SamplesRNAseq characterization of gene expression changes 72 hours after genomic excision of Cebpa in murine hematopoietic progenitors from Cebpaf/f;CreER mice transformed by Hoxa9/Meis1. In the presence of tamoxifen (4OHT), Cre-ER localizes to the nucleus of cells allowing for excision of Cebpa and loss of C/EBPa protein levels. Loss of C/EBPa leads to a decrease in cellular proliferation. Overall design: Examination of gene expression by RNAseq in two conditions in biological replicates.
C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis.
No sample metadata fields
View SamplesCharacterization of gene expression changes 72 hours after withdrawal of tamoxifen in murine hematopoietic progenitors transformed by Hoxa9-ER/Meis1 using RNAseq. In the presence of tamoxifen (4OHT), Hoxa9-ER localizes to the nucleus of cells allowing for transformation, while withdrawal of 4OHT (culture in EtOH) leads to loss of nuclear Hoxa9-ER. Loss of Hoxa9-ER leads to a decrease in cellular proliferation and differentiation along the myeloid lineage. Overall design: Examination of gene expression by RNAseq in two conditions in biological replicates.
C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis.
No sample metadata fields
View Samples