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GSE15299
Mus musculus, Homo sapiens
24 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To elucidate mechanisms of cancer progression, we generated inducible human neoplasia in 3-dimensionally intact epithelial tissue. Gene expression profiling of both epithelia and stroma at specific time points during tumor progression revealed sequential enrichment of genes mediating discrete biologic functions in each tissue compartment. A core cancer progression signature was distilled using the increased signaling specificity of downstream oncogene effectors and subjected to network modeling. Network topology predicted that tumor development depends upon specific ECM-interacting network hubs. Blockade of one such hub, the b1 integrin subunit, disrupted network gene expression and attenuated tumorigenesis in vivo. Thus, integrating network modeling and temporal gene expression analysis of inducible human neoplasia provides an approach to prioritize and characterize genes functioning in cancer progression.
Publication Title
Modeling inducible human tissue neoplasia identifies an extracellular matrix interaction network involved in cancer progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Stem cell fate is governed by the integration of intrinsic and extrinsic positive and negative signals upon inherent transcriptional networks. To identify novel embryonic stem cell (ESC) regulators and assemble transcriptional networks controlling ESC fate, we performed temporal expression microarray analyses of ESCs following the initiation of commitment and integrated these data with known genome-wide transcription factor binding. Effects of forced under- or over-expression of predicted novel regulators, defined as differentially expressed genes with potential binding sites for known regulators of pluripotency, demonstrated greater than 90% correspondence with predicted function, as assessed by functional and high content assays of self-renewal. We next assembled 43 theoretical transcriptional networks in ESCs, 82% (23 out of 28 tested) of which were supported by analysis of genome-wide expression in Oct4 knockdown cells. By using this integrative approach we have, for the first time, formulated novel networks describing gene repression of key developmental regulators in undifferentiated ESCs and successfully predicted the outcomes of genetic manipulation of these networks.
Publication Title
Prediction and testing of novel transcriptional networks regulating embryonic stem cell self-renewal and commitment.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 86 Downloadable Samples
- Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Disparate Oxidant-related Gene Expression of Human Small Airway Epithelium Compared to Autologous Alveolar Macrophages in Response to the In Vivo Oxidant Stress of Cigarette Smoking
Publication Title
Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Effector cells for adoptive immunotherapy can be generated by in vitro stimulation of nave or memory subsets of CD8+ T cells. While the characteristics of CD8+ T cell subsets are well defined, the heritable influence of those populations on their effector cell progeny is not well understood. We studied effector cells generated from nave or central memory CD8+ T cells and found that they retained distinct gene expression signatures and developmental programs. Effector cells derived from central memory cells tended to retain their CD62L+ phenotype, but also to acquire KLRG1, an indicator of cellular senescence. In contrast, the effector cell progeny of nave cells displayed reduced terminal differentiation, and, following infusion, they displayed greater expansion, cytokine production, and tumor destruction. These data indicate that effector cells retain a gene expression imprint conferred by their nave or central memory progenitors, and they suggest a strategy for enhancing cancer immunotherapy.
Publication Title
Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Microarray was used to identify differential gene expression pattern in Barrett's esophagus (BE), compared to the normal adjacent epithelia gastric cardia (GC) and normal squamous esophagus (NE)
Publication Title
Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Illumina HiSeq 2000
Description
Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. Overall design: RNA profiles in Striatum of WT and R6/1 mice by deep sequencing using Illumina HiSeq 2000.
Publication Title
Altered enhancer transcription underlies Huntington's disease striatal transcriptional signature.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative genomics positions MKRN1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In embryonic stem cell (ESCs), gene regulatory networks (GRNs) coordinate gene expression to maintain ESC identity; however, the complete repertoire of factors that regulate the ESC state are not fully understood. Our previous temporal microarray analysis of ESC commitment identified the E3 Ubiquitin Ligase Protein Makorin-1 (MKRN1) as a potential novel component of the ESC GRN. Here, using multilayered systems-level analyses we compiled a MKRN1-centered interactome in undifferentiated ESCs at the proteomic and ribonomic level. Proteomic analyses revealed that MKRN1 is a novel RNA-binding protein that exists within messenger ribonucleoprotein (mRNP) complexes in undifferentiated ESC populations. In accordance with its presence in mRNPs, MKRN1 is mobilized to stress granules (SG) upon arsenite-induced stress, yet MKRN1 is not required for SG formation. RIP-chip analysis revealed that MKRN1 associates with mRNAs encoding functionally related regulatory proteins involved in diverse processes such as cell differentiation, apoptosis, or secreted proteins. Thus, our unbiased systems level analyses supports a role for MKRN1 as a novel RNA-binding protein and a potential gene regulatory protein within the ESC GRN.
Publication Title
Integrative genomics positions MKRN1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In embryonic stem cell (ESCs), gene regulatory networks (GRNs) coordinate gene expression to maintain ESC identity; however, the complete repertoire of factors that regulate the ESC state are not fully understood. Our previous temporal microarray analysis of ESC commitment identified the E3 Ubiquitin Ligase Protein Makorin-1 (MKRN1) as a potential novel component of the ESC GRN. Here, using multilayered systems-level analyses we compiled a MKRN1-centered interactome in undifferentiated ESCs at the proteomic and ribonomic level. Proteomic analyses revealed that MKRN1 is a novel RNA-binding protein that exists within messenger ribonucleoprotein (mRNP) complexes in undifferentiated ESC populations. In accordance with its presence in mRNPs, MKRN1 is mobilized to stress granules (SG) upon arsenite-induced stress, yet MKRN1 is not required for SG formation. RIP-chip analysis revealed that MKRN1 associates with mRNAs encoding functionally related regulatory proteins involved in diverse processes such as cell differentiation, apoptosis, or secreted proteins. Thus, our unbiased systems level analyses supports a role for MKRN1 as a novel RNA-binding protein and a potential gene regulatory protein within the ESC GRN.
Publication Title
Integrative genomics positions MKRN1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human and mouse embryonic stem cells (ESCs) are derived from blastocyst stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by exogenous induction of Oct4, Klf4 and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase (ERK) pathway. Forskolin, a protein kinase A pathway agonist that induces Klf4 and Klf2 expression, can transiently substitute for the requirement for ectopib transgene expression. In contrast to conventional human ESCs, these epigenetically converted cells have growth properties, an X chromosome activation state (XaXa), a gene expression profile, and signaling pathway dependence that are highly similar to that of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of nave human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans, and may open up new opportunities for patient-specific, disease-relevant research.
Publication Title
Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs.
Sample Metadata Fields
Specimen part
View Samples