Activation of the MLL-ENL-ERtm oncogene initiates aberrant proliferation of myeloid progenitors. Here, we show induction of a fail-safe mechanism mediated by the DNA damage response (DDR) machinery that results in activation of the ATR/ATM-Chk1/Chk2-p53/p21 checkpoint and cellular senescence at early stages of cellular transformation caused by a regulatable MLL-ENL-ERtm in mice. Furthermore, we identified the transcription program underlying this intrinsic anti-cancer barrier, and DDR-induced inflammatory regulators that fine-tune the signaling towards senescence, thereby modulating the fate of MLL-ENL-immortalized cells in a tissue-environment-dependent manner. Our results indicate that DDR is a rate-limiting event for acquisition of stem cell-like properties in MLL-ENL-ERtm-mediated transformation, as experimental inhibition of the barrier accelerated the transition to immature cell states and acute leukemia development.
DNA damage response and inflammatory signaling limit the MLL-ENL-induced leukemogenesis in vivo.
Specimen part, Disease stage
View SamplesThe goal of this study was to determine developmental differences in gene expression between left and right ventricle, and to assess the differential effect of altered hemodynamic loading on left and right ventricle. Chick ventricles from different developmental stages were isolated for assessment of normal developmental profiles. Conotruncal banding or partial ligation of the left atrial appendage was performed in ovo at embryonic day 4 and ventricles were isolated at embryonic day 5 (banding) or 8 (ligation) for assessment of altered loading effects.
Microarray analysis of normal and abnormal chick ventricular myocardial development.
Specimen part
View SamplesBisphenol S (BPS) is widely used to replace earlier-eliminated BPA. We evaluated the effect of acute in vivo BPS exposure on oocyte quality using eight-weeks-old ICR female mice (N = 15 per experimental group), exposed to vehicle or BPS1-BPS4 (0.001, 0.1, 10, and 100 ng BPS x g bw-1 x day-1, respectively). Oocytes were isolated and matured in vitro. Thereafter, we observed that BPS exposure increases aberrant spindle formation in mature oocytes and induces DNA damage. Moreover, BPS3 significantly increases chromatin repressive marks 5-methyl cytosine (5meC) and H3K27me2 in immature oocytes. In the BPS2 group (0.1 ng x g bw-1 x day-1), the increase in 5meC arises during oocyte maturation. Transcriptome analysis shows differential expression of early embryonic development transcripts in BPS2-exposed oocytes. These findings indicate that the biological effect of BPS is non-monotonic, affecting oocyte quality even at concentrations that are orders of magnitude below those measured in humans.
Acute low-dose bisphenol S exposure affects mouse oocyte quality.
Sex, Age, Specimen part, Treatment
View SamplesSex chromosomes are characterized by a non-random content of genes with preferential expression in one sex. The mechanisms which are responsible for this phenomenon are, however, largely unresolved. To elucidate selective forces shaping the Z chromosome gene content in chicken, we analyzed microarray data from adult and embryonic gonads (the latter already available in GEO Series GSE8693).
No associated publication
No sample metadata fields
View SamplesFormins (FH2 proteins) are a family of evolutionarily conserved proteins involved in many aspects of cytoskeletal organization and signalling, shown in some cases to participate in transcriptional regulation in metazoans. However, nothing is known about their possible involvement in the regulation of gene expression in angiosperms.
No associated publication
Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression.
Sex, Age, Cell line
View SamplesTo define the role of microRNAs and their mRNA targets in emphysema severity in COPD patients.
No associated publication
Cell line
View SamplesElevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lymphocytic leukemia (B-CLL). In this study, we present evidence that MYB (v-myb myeloblastosis viral oncogene homolog) is overexpressed in a subset of B-CLL patients. MYB physically associates with the promoter of MIR155 host gene (MIR155HG, also known as BIC, B-cell integration cluster) and stimulates its transcription. This coincides with the hypermethylated histone H3K4 residue and spread hyperacetylation of H3K9 at MIR155HG promoter. Our data provide evidence of oncogenic activities of MYB in B-CLL that include its stimulatory role in MIR155HG transcription.
MYB transcriptionally regulates the miR-155 host gene in chronic lymphocytic leukemia.
Specimen part, Disease, Disease stage
View SamplesThis dataset contains 9 Illumina array spots representing 3 different treatment conditions of human mesenchymal cells. First two conditions in quadruplicate and third condition on single array. The data are intended to support blima package as testing data included in blimaTestingData package available at https://bitbucket.org/kulvait/blima page. The package was developed to make analysis of Illumina bead level data possible without summarizing them to the level of probes prior to differential expression testing.
No associated publication
No sample metadata fields
View SamplesComparison of CLL and MCL primary cells obtained from a patient with MCL variant Richter syndrome
Mantle cell lymphoma-variant Richter syndrome: Detailed molecular-cytogenetic and backtracking analysis reveals slow evolution of a pre-MCL clone in parallel with CLL over several years.
Specimen part, Disease, Disease stage
View Samples