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Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis.
Specimen part
View SamplesDNA methylation is tightly regulated throughout mammalian development and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CpG islands and promoters from aberrant DNA methylation. In this study, we present a novel Tet2-dependent leukemia mouse model that closely recapitulates gene expression profiles and hallmarks of human AML1-ETO induced AML. Using this model, we show that the primary effect of Tet2 loss in pre-leukemic hematopoietic cells is progressive and widespread DNA hypermethylation affecting up to 25% of active enhancer elements. In contrast, CpG island and promoter methylation does not change in a Tet2-dependent manner, but increase relative to population doublings. We confirm this specific enhancer hypermethylation phenotype in human AML patients with TET2 mutations. Analysis of immediate gene expression changes reveals rapid deregulation of a large number of genes implicated in tumorigenesis, including many downregulated tumor suppressor genes. Hence, we propose that TET2 prevents leukemic transformation by protecting enhancers from aberrant DNA methylation, and that it is the combined silencing of several tumor suppressor genes in TET2-mutated hematopoietic cells that contribute to increased stem cell proliferation and leukemogenesis.
Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis.
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View SamplesHigh-throughput RNA sequencing (RNA-seq) is now the standard method to determine differential gene expression. Here, a 48 replicate, two condition RNA-seq experiment was designed specifically to test assumptions about RNA-seq read count variability models and the performance of methods for differential gene expression analysis by RNA-seq. Samples were run on an Illumina HiSeq for 50 cycles single-end and included ERCC RNA spike-ins. The high-replicate data allowed for strict quality control and screening of 'bad' replicates. The experiment allowed the effect of bad replicates to be assessed as well as providing guidelines for the number of replicates required for differential gene expression analysis and the most appropriate statistical tools. The mapping between technical replicates and biological replicates is provided via FigShare http://dx.doi.org/10.6084/m9.figshare.1416210 The gene read counts are also available on FigShare: https://dx.doi.org/10.6084/m9.figshare.1425503 https://dx.doi.org/10.6084/m9.figshare.1425502
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No sample metadata fields
View Sampleswe construct a comprehensive mouse transcriptomic BodyMap across 17 tissues of six-weeks old C57BL/6JJcl mice using RNA-seq. We find different expression patterns between protein-coding and non-coding genes. Liver and adrenal gland expressed the least complex transcriptome, whereas testis and ovary harbor more complex transcriptome than other tissues. We report a comprehensive list of tissue-specific genes across 17 tissues. Our study provides a unique resource of mouse gene-expression profiles, which is helpful for further biomedical research.
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Sex, Specimen part, Cell line
View SamplesTo investigate the random X chromosome inactivation in vivo, we used allelic-specific RNA sequencing of single cells in mouse model. The intercross was between two genetically distant strains, C57BL/6 and PWK/Ph.
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Sex, Specimen part, Disease, Disease stage, Cell line
View SamplesTo obtain a comprehensive understanding of transcriptomic reprogramming under salt stress, we performed whole genome RNA sequencing on salt-treatment soybean seedlings, on two tissues in a time-course experiment (0h, 1h, 2h, 4 h, 24h and 48h). This time series dataset enables us to identify important hubs and connection of gene expressions. We highlighted the analysis of phytohormone signaling pathways and their possible cross-talking. Gene expression regulation also controls adjustment of carbon and nitrogen metabolism. In general, the treated seedlings had turned off the photosynthetic mechanism and enhanced sugar catabolism to provide energy for survival. Primary nitrogen assimilation was shut down while re-distribution of nitrogen resources was activated. Genes for other protective mechanisms were also induced, including structural modification, ion-sequestering, and scavenging of reactive oxygen species.
No associated publication
Specimen part, Disease, Treatment
View SamplesIn order to study translational control by cis-regulatory elements in untranslated region of mRNA, ribosome profiling assays during different developmental stages of Drosophila melanogaster and in S2 cells cultured in normal and stressful conditions were performed.
No associated publication
Sex, Specimen part, Cell line
View SamplesPorcine meat production is determined by total myofiber number, while during embryonic stages, total myofiber number is determined by primary myofiber number. Thus, primary myofiber is a crucial determinant factor of porcine adult meat production. Understanding the molecular mechanisms of distinct primary myofiber formation time in pig breeds with different meat production will help to improve pig meat production by genetic methods and benefit the researches concerning muscle development. In this study RNA-seq to uncover the molecular mechanisms of distinct primary myofiber formation time in pig breeds with different meat production (Landrace and Wuzhishan) by using longissimus dorsi muscle (LDM) samples during 3 early embryonic stages (18,21,28 dpc).
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Sex, Specimen part
View SamplesThe goals of this study is to determine alternative splicing events in Arabidopsis thaliana.
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Specimen part
View SamplesThe CLAVATA1(CLV1)-related Leucine-rich repeat receptor-like kinase BAM3 was previously reported to function additively to BAM1/2 in other aspects of plant development. Here we reported the important role of BAM3 in anther development. We demonstrated that in the anther, bam3-2 single mutant exhibited delayed tapetal degradation and a more extensively covered surface through cell biological analyses. Further transcriptomic studies revealed that 813 genes significantly expressed at the RNA level in the bam3-2 mutant compared with wild-type, which were enriched in pollen exine formation, lipid metabolism, lipid transfer, and proteolysis. Moreover, an intersection analysis of significantly regulated genes in bam3-2, DN-CLE19 and ams revealed BAM3, CLE19 and AMS commonly affected the expression level of many genes, especially genes invovled in pollen development such as CYP703A2?LAP6?TKPR2?CYP703B1?MS2?WBC27?MEE48?QRT3?LAP5?DRL1 and MYB103. These results suggested that BAM3 is a crucial executor during tapetum degradation and pollen exine formation and probably takes part in the CLE19-AMS signaling pathway during anther development process.
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Sex, Specimen part
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