This SuperSeries is composed of the SubSeries listed below.
Dual role of FoxA1 in androgen receptor binding to chromatin, androgen signalling and prostate cancer.
Specimen part, Cell line
View SamplesWe report the dual role of FoxA1 in androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell line LNCaP-1F5 using ChIP-sequencing. Depletion of FoxA1 reprograms both androgen and glucocorticoid receptor recruitment and subsequent gene expression. The ChIP-seq has been performed using AR, FoxA1, GR, H3K4me2 antibodies. We have also mapped the DNaseI-hypersensitive sites (DHS) using deep sequencing.
Dual role of FoxA1 in androgen receptor binding to chromatin, androgen signalling and prostate cancer.
Cell line
View SamplesWe utilized RNA-Seq on rat Schwann (S16) cells to determine global gene expression. This information was generated as part of a larger effort to characterize cis-regulatory elements and global gene expression within Schwann cells. To achieve this, we generated RPKM values across two independent biological replicates. This dataset was also used to predict cis-regulatory element function on genes following CRISPR knockout studies. Overall design: Performed two technical replicates of RNA-Seq on two independent biological replicates of S16 cells
A genome-wide assessment of conserved SNP alleles reveals a panel of regulatory SNPs relevant to the peripheral nerve.
No sample metadata fields
View SamplesDigital gene expression tag profiling of P19CL6 cell model during differentiation to cardiomyocytes Overall design: Four replicates were anlyzed at five time-points during differentiation; day 1, day 4, day 7, day 10 and day 14. Spontanously beating cardiomyocytes was observed at day 14 Spreadsheet with Log2 difference expression values is filtered by FDR and thus incomplete.
TGF-β signaling is associated with endocytosis at the pocket region of the primary cilium.
Cell line, Subject, Time
View SamplesEmbryonic stem cells (ESCs) maintain high genomic plasticity, essential for their capacity to enter diverse differentiation pathways. Post-transcriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2BK120ub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of long genes during ESC differentiation. Furthermore, we identify USP44 as a deubiquitinase whose downregulation by differentiation signals contributes to the increase in H2BK120ub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner.
RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation.
Cell line, Treatment
View SamplesInvasion of lymphatic vessels is a key step in the metastasis of primary tumour cells to draining lymph nodes. Recent evidence indicates that such metastasis can be facilitated by tumour lymphangiogenesis, although it remains unclear whether this is a consequence of increased lymphatic vessel numbers or alteration in the properties of the vessels themselves. Here we have addressed this important question by comparing the RNA profile of normal dermal lymphatic endothelial cells (LEC) with those isolated from tumours of murine T-241/VEGF-C metastatic fibrosarcoma. Our findings reveal significant changes in the expression of some 792 genes in tumour lymphatics ( 2 fold up/downregulation, p 0.05), involving particularly transcripts associated with junctional adhesion, immunomodulation, extracellular matrix and vessel growth/patterning, several of which we have confirmed by RT-PCR and/or immunohistochemistry. Interestingly, this altered phenotype could not be attributed solely to VEGF-C induced lymphoproliferation, as no similar change in gene expression was reported when human LEC were cultured with VEGF-C in vitro. Moreover, we show that a key protein upregulated in the mouse model, namely the tight junction protein Endothelial Cell Specific Adhesion Molecule (ESAM), is similarly upregulated in tumour lymphatic vessels from 2/2 patients with head and neck squamous cell carcinoma and 4/4 patients with aggressive bladder carcinoma. These findings demonstrate a previously unrecognized influence of tumour environment on lymphatic gene expression and identify candidate tumour specific vessel markers that may prove valuable for either prognosis or therapy.
A novel gene expression profile in lymphatics associated with tumor growth and nodal metastasis.
No sample metadata fields
View SamplesUbiquitination is a post-translational mechanism of control of diverse cellular processes. We focus here on the ubiquitin ligase Fbw7, a recently identified hematopoietic tumor suppressor that can target for degradation several important oncogenes including Notch1, c-Myc and cyclin E. We have generated conditional Fbw7 knock-out animals and inactivated the gene in hematopoietic stem cells (HSC) and their differentiated progeny. Deletion of Fbw7 specifically and rapidly affects the HSC compartment in a cell-autonomous manner. Fbw7-/- HSCs show defective maintenance of quiescence, leading to impaired self-renewal and a severe loss of competitive repopulating capacity. Furthermore, Fbw7-/- HSC are unable to colonize the thymus leading to a profound depletion of T cell progenitors. Deletion of Fbw7 in bone marrow stem cells and progenitors leads to the stabilization of c-Myc, a transcription factor previously implicated in HSC self-renewal. On the other hand, neither Notch1 nor cyclin E are stabilized in the bone marrow of Fbw7 deficient mice. Genome-wide transcriptome studies of Fbw7-/- HSC and hematopoietic progenitors indicate that Fbw7 controls, through the regulation of HSC cell cycle entry, the global transcriptional signature that is associated with the quiescent, self-renewing HSC phenotype.
Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.
Specimen part, Disease
View SamplesTodays diagnostic tests for multiple myeloma (MM) reflect the criteria of the updated WHO classification based on biomarkers and clinicopathologic heterogeneity. To that end, we propose a new subtyping of myeloma plasma cells (PC) by B-cell subset associated gene signatures (BAGS), from the normal B-cell hierarchy in the bone marrow (BM). To do this, we combined FACS and GEP data from normal BM samples to generate classifiers by BAGS for the PreBI, PreBII, immature (Im), nave (N), memory (M) and PC subsets. The resultant tumor assignments in available clinical datasets exhibited similar BAGS subtype frequencies in four cohorts across 1302 individual cases. The prognostic impact of BAGS was analyzed in patients treated with high dose melphalan as first line therapy in three prospective trials: UAMS, HOVON65/GMMG-HD4 and MRC Myeloma IX with Affymetrix U133 plus 2.0 microarray data available from diagnostic myeloma PC samples. The BAGS subtypes were significantly associated with progression free (PFS) and overall survival (OS) (PFS, P=3.05e06 and OS, P=1.06e11) in a meta-analysis of 926 pts. The major impact was observed within the PreBII and M subtypes conferred with significant inferior prognosis compared to the Im, N and PC subtypes. Cox proportional hazard meta-analysis documented that the BAGS subtypes added significant and independent prognostic information to the TC classification system and ISS staging. BAGS subtype analysis identified transcriptome differences and a number of novel differentially spliced genes. We have identified hierarchal subtype differences in the myeloma plasma cells, with prognostic impact. This observation support an acquired reversible B-cell trait and phenotypic plasticity as a hallmark, also in MM.
A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.
Specimen part
View SamplesTodays diagnostic tests for multiple myeloma (MM) reflect the criteria of the updated WHO classification based on biomarkers and clinicopathologic heterogeneity. To that end, we propose a new subtyping of myeloma plasma cells (PC) by B-cell subset associated gene signatures (BAGS), from the normal B-cell hierarchy in the bone marrow (BM). To do this, we combined FACS and GEP data from normal BM samples to generate classifiers by BAGS for the PreBI, PreBII, immature (Im), nave (N), memory (M) and PC subsets. The resultant tumor assignments in available clinical datasets exhibited similar BAGS subtype frequencies in four cohorts across 1302 individual cases. The prognostic impact of BAGS was analyzed in patients treated with high dose melphalan as first line therapy in three prospective trials: UAMS, HOVON65/GMMG-HD4 and MRC Myeloma IX with Affymetrix U133 plus 2.0 microarray data available from diagnostic myeloma PC samples. The BAGS subtypes were significantly associated with progression free (PFS) and overall survival (OS) (PFS, P=3.05e06 and OS, P=1.06e11) in a meta-analysis of 926 pts. The major impact was observed within the PreBII and M subtypes conferred with significant inferior prognosis compared to the Im, N and PC subtypes. Cox proportional hazard meta-analysis documented that the BAGS subtypes added significant and independent prognostic information to the TC classification system and ISS staging. BAGS subtype analysis identified transcriptome differences and a number of novel differentially spliced genes. We have identified hierarchal subtype differences in the myeloma plasma cells, with prognostic impact. This observation support an acquired reversible B-cell trait and phenotypic plasticity as a hallmark, also in MM.
A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.
Disease
View Samples