Analysis of transcriptional differences between control and RA-treated cells during cardiac differentiation. The hypothesis tested in these samples is that addition of RA during differentiation towards atrial-like cardiomyocytes while control cells treated with DMSO result in ventricular-like cardiomyocytes. Overall design: NKX2.5 (eGFP/w)-hESCs were differentiated to cardiomyocytes with spin EB protocol, with the addition of RA or DMSO. Cells were sorted at day-31 based on GFP resulting in CTplus, CTminus, RAplus or RAminus goups. RNA was isolated from each of these fractions for sequencing.
KeyGenes, a Tool to Probe Tissue Differentiation Using a Human Fetal Transcriptional Atlas.
No sample metadata fields
View SamplesIn order to identify relevant, molecularly defined subgroups in Multiple Myeloma (MM), gene expression profiling (GEP) was performed on purified CD138+ plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/ GMMG-HD4 trial using Affymetrix GeneChip U133 plus 2.0 arrays. Hierarchical clustering identified 10 distinct subgroups. Using this dataset as training data, a prognostic signature was built. The dataset consists of 282 CEL files previously used in the hierarchical clustering study of Broyl et al (Blood, 116(14):2543-53, 2010) outlined above. To this set 8 CEL-files/gene expression profiles were added. Using this set of 290 CEL-files, a prognostic signature of 92 genes (EMC-92-genesignature) was generated by supervised principal components analysis combined with simulated annealing (Kuiper et al.).
Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.
Sex
View SamplesThe second trimester fetal transcriptome can be assessed based on cell-free RNA found within the amniotic fluid supernatant. The objective of this study was to compare the suitability of two technologies for profiling the human fetal transcriptome: RNA-Seq and expression microarray. Comparisons were based on total numbers of gene detected, rank-order gene expression, and functional genomic analysis.
RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.
Sex
View SamplesMonoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE, and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells (Nag et al. Elife. 2013 Dec 31;2:e01256). Here, we use murine cells to establish that this chromatin signature is conserved between mouse and human, and is associated with MAE in every tested cell type. Our analyses reveal extensive conservation in the identity of MAE genes between the two species. By applying MAE chromatin signature analysis to a large number of cell and tissue types, we show that the MAE state remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity. Overall design: PolyA RNA purification and subsequent high-throughput sequencing were performed on two independent B-lymphoid clonal cell line, derived from 129S1/SvImJ x CAST/EiJ F1 mice and immortalized with Abelson murine leukemia virus, and on two independent fibroblast clonal cell lines, derived from 129S1/Sv x CAST/EiJ F1 and immortalized with SV40.
Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types.
No sample metadata fields
View SamplesNotch signaling plays both oncogenic and tumor suppressor roles, depending on cell type. In contrast to T cell acute lymphoblastic leukemia (T-ALL), where Notch activation promotes leukemogenesis, induction of Notch signaling in B-ALL leads to growth arrest and apoptosis. The Notch target Hairy/Enhancer of Split1 (HES1) is sufficient to reproduce this tumor suppressor phenotype in B-ALL, however the mechanism is not yet known. Here we report that HES1 regulates pro-apoptotic signals via the novel interacting protein Poly ADP-Ribose Polymerase1 (PARP1) in a cell type-specific manner. The interaction of HES1 with PARP1 inhibits HES1 function, induces PARP1 activation and results in PARP1 cleavage in B-ALL. HES1-induced PARP1 activation leads to self-ADP ribosylation of PARP1, consumption of NAD+, diminished ATP levels, and translocation of the Apoptosis Inducing Factor (AIF) from mitochondria to the nucleus, resulting in apoptosis in B-ALL, but not T-ALL. Importantly, induction of Notch signaling via the Notch agonist peptide DSL can reproduce these events and leads to BALL apoptosis. The novel interaction of HES1 and PARP1 in B-ALL modulates the function of the HES1 transcriptional complex and signals through PARP1 to induce apoptosis. This mechanism reveals a cell type-specific pro-apoptotic pathway which may lead to Notch agonist-based cancer therapeutics.
Notch/HES1-mediated PARP1 activation: a cell type-specific mechanism for tumor suppression.
Specimen part
View SamplesThroughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to evaluate potential heterogeneity in the NSC pool, we microdissected the dorsal and lateral SVZ at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors influenced NSC specification indicating that the fate of regionalized postnatal SVZ NSCs can be readily modified . These findings reveal functional heterogeneity of NSCs in the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts.
Transcriptional Hallmarks of Heterogeneous Neural Stem Cell Niches of the Subventricular Zone.
Specimen part
View SamplesExpression of mutant lamins in human muscle causes muscular dystrophy. We have generated a drosophila model that expresses mutant lamins, modeled after those that cause disease in humans.
Myopathic lamin mutations cause reductive stress and activate the nrf2/keap-1 pathway.
Specimen part
View SamplesThe purpose of this study was to characterise the effects of trastuzumab and pertuzumab, either as single agents or as combination therapy on gene and protein expression in human ovarian cancer in vivo. Illumina BeadChips were used to profile the transcriptome after four days treatment of SKOV3 tumor xenografts. Although genes involved with HER2, MAP-kinase and p53 signaling pathways were commonly induced by all treatments, a greater number and variety of genes were differentially expressed by the complementary combination therapies compared to either drug on its own. The protein level of the CDK-inhibitors p21 and p27 were increased in response to both agents alone and further by the combination; pERK signaling was inhibited by all treatments; but only pertuzumab alone inhibited pAkt signaling. The expression of proliferation, apoptosis, cell division and cell cycle markers was distinct in a panel of primary ovarian cancer xenografts, suggesting heterogeneity of response in ovarian cancer and the need to establish biomarkers of response.
Defining the molecular response to trastuzumab, pertuzumab and combination therapy in ovarian cancer.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The Small Molecule Hyperphyllin Enhances Leaf Formation Rate and Mimics Shoot Meristem Integrity Defects Associated with AMP1 Deficiency.
Specimen part, Treatment
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