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SRP007403
Homo sapiens
2 Downloadable Samples
IlluminaGenomeAnalyzer
Description
Regulation of cell-cell junction formation and regulation of cell migration were enriched among EMT (Epithelial-Mesenchymal Transition)-associated alternatively splicing events. Our analysis suggested that most EMT-associated alternative splicing events are regulated by one or more members of the RBFOX, MBNL, CELF, hnRNP or ESRP classes of splicing factors. The EMT alternative splicing signature was confirmed in human breast cancer cell lines, which could be classified into basal and luminal subtypes based exclusively on their EMTassociated splicing pattern. Expression of EMT-associated alternative mRNA transcripts was also observed in primary breast cancer samples, indicating that EMT-dependent splicing changes occur commonly in human tumors. The functional significance of EMT-associated alternative splicing was tested by expression of the epithelial-specific splicing factor ESRP1 or depletion of RBFOX2 in mesenchymal cells, both of which elicited significant changes in cell morphology and motility towards an epithelial phenotype, suggesting that splicing regulation alone can drive critical aspects of EMT-associated phenotypic changes. The molecular description obtained here may aid in the development of new diagnostic and prognostic markers for analysis of breast cancer progression. Overall design: Examination of transcriptomes of HMLE/Twist-ER before and after induction of EMT by tamoxifen
Publication Title
An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 8 Downloadable Samples
Affymetrix Rat Clariom S Assay (clariomsrat)
Description
The study evaluates potential protective effects of cerium oxide nanoparticles (nanoceria) against oxidative stress in muscle tissue, both on ground and in space
Publication Title
Modulation of gene expression in rat muscle cells following treatment with nanoceria in different gravity regimes.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
While the hypothalamo-pituitary-adrenal axis (HPA) activates a general stress response by increasing glucocorticoid (Gc) synthesis, biological stress resulting from infections triggers the inflammatory response through production of cytokines. The pituitary gland integrates some of these signals by responding to the pro-inflammatory cytokines IL6 and LIF and to a negative Gc feedback loop. The present work used whole-genome approaches to define the LIF/STAT3 regulatory network and to delineate cross-talk between this pathway and Gc action. Genome-wide ChIP-chip identified 3 449 STAT3 binding sites, whereas 2 396 genes regulated by LIF and/or Gc were found by expression profiling. Surprisingly, LIF on its own changed expression of only 85 genes but the joint action of LIF and Gc potentiated the expression of more than a thousand genes. Accordingly, activation of both LIF and Gc pathways also potentiated STAT3 and GR recruitment to many STAT3 targets. Our analyses revealed an unexpected gene cluster that requires both stimuli for delayed activation: 83% of the genes in this cluster are involved in different cell defense mechanisms. Thus, stressors that trigger both general stress and inflammatory responses lead to activation of a stereotypic innate cellular defense response.
Publication Title
Regulatory network analyses reveal genome-wide potentiation of LIF signaling by glucocorticoids and define an innate cell defense response.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hypoxia, which characterizes most tumor tissues, can alter the function of different immune cell types, favoring tumor escape mechanisms. In this study, we show that hypoxia profoundly acts on NK cells by influencing their transcriptome, affecting their immunoregulatory functions, and changing the chemiotactic responses of different NK cell subsets.
Publication Title
Hypoxia Modifies the Transcriptome of Human NK Cells, Modulates Their Immunoregulatory Profile, and Influences NK Cell Subset Migration.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2000
Description
Pitx1, critical regulator of a limited hindlimb-specific gene network, targets the limb development program common to both fore- and hindlimbs in order to implement hindlimb-specific limb morphology. Overall design: The gene regulatory networks governing forelimb vs. hindlimb development in mouse were investigated using expressing profiling of morphologically stage-matched e10.5 forelimbs and e11.0 hindlimbs, ChIPseq of chromatin marks, and ChIPseq of limb-specific transcription factors Pitx1 and Tbx5. The makeup of the Pitx1-directed components of the hindlimb gene network were investigated using expression profiling of Pitx1 null hindlimbs at two stages (e11.0 and e11.5).
Publication Title
Regulatory integration of Hox factor activity with T-box factors in limb development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
Deployment of a cell-specifying enhancer repertoire by the pioneer factor Pax7 The establishment and maintenance of cell identity depends on implementation of stable cell-specific chromatin landscapes. Pioneer transcription factors establish new cell fate competences by triggering chromatin remodeling during development. Here, we used pituitary cell specification to define the salient features of pioneer action. Comparison of purified pituitary cells of different lineages showed that chromatin accessibility differs at enhancers rather than promoters. The pioneer factor Pax7 specifies one pituitary lineage identity by opening a specific repertoire of enhancers that are distinct from the myogenic targets of Pax7. Pax7 binds its pioneer targets rapidly and days before chromatin remodeling and gene activation. Finally, enhancers opened by Pax7-dependent chromatin remodeling exhibit loss of DNA methylation and they acquire long term epigenetic memory. The present work identifies enhancer pioneering as a critical feature for cell fate specification and maintenance. Overall design: RNA extraction followed by high throughput sequencing (RNA-seq)
Publication Title
Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of cell fate.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
The combinatorial expression of the Hox genes along the body axes, referred to as the HOX code, is a major determinant of cell fate and plays a prevailing role in generating the animal body plan. In developing limb buds, the paralogous group 13 genes of the HoxA and HoxD clusters are essential for patterning the distal-most limb structures, the digits. Inactivation of HOXA13 and HOXD13 transcription factors (HOX13) leads to complete digit agenesis in mice, but how HOX13 regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here we performed genome-wide profiling of HOX13 by chromatin immunoprecipitation and analyzed the transcriptome and chromatin state of wild type early and late-distal limb buds, as well as Hoxa13-/-;Hoxd13-/- compound mutant limb buds. Our results show that inactivation of HOX13 impairs the activation and repression of putative cis-regulatory modules specific to the late-distal limb cells. Loss of HOX13 also disrupts the specific, spatial patterning of gene expression along the proximal-distal axis of the developing limb buds. These results show that proper termination of the early limb transcriptional program and activation of the late-distal limb program are coordinated by the dual action of HOX13 on cis-regulatory modules. Overall design: Totla mRNAs from dissected distal parts of e11.5 forelimb, of wild-type as well as Hoxa13-/-;Hoxd13-/- mice
Publication Title
Regulatory integration of Hox factor activity with T-box factors in limb development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Cells from 2 FL patients and 1 FL cell line were cultured for up to 48h, with no stroma or on top of HK cells pre-establised layers. RNA from FL cells was isolated after 24 and 48h of culture
Publication Title
Disruption of follicular dendritic cells-follicular lymphoma cross-talk by the pan-PI3K inhibitor BKM120 (Buparlisib).
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 115 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Renal failure is characterized by important biological changes resulting in profound pleomorphic physiological effects termed uremia, whose molecular causation is not well understood. The data was used to study gene expression changes in uremia using whole genome microarray analysis of peripheral blood from subjects with end-stage renal failure (n=63) and healthy controls (n=20) to obtain insight into the molecular and biological causation of this syndrome.
Publication Title
Alteration of human blood cell transcriptome in uremia.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Race
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) <= 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.
Publication Title
White blood cell differentials enrich whole blood expression data in the context of acute cardiac allograft rejection.
Sample Metadata Fields
No sample metadata fields
View Samples