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accession-icon GSE56897
The transcription factor GATA6 allows self-renewal of colon adenoma stem cells by repressing BMP gene expression
  • organism-icon Homo sapiens
  • sample-icon 14 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression.

Sample Metadata Fields

Specimen part, Cell line

View Samples
accession-icon GSE56895
Identification of GATA6 target genes in LS174T colorectal cancer cells using gene expression arrays
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 competes with beta-catenin/TCF4 for binding to a distal regulatory region of the BMP4 locus that has been previously linked to increased susceptibility to develop CRC. Hence, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation.

Publication Title

The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression.

Sample Metadata Fields

Specimen part, Cell line

View Samples
accession-icon GSE56896
Identification of beta-cetenin/TCF4 target genes in LS174T colorectal cancer cells using gene expression arrays
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 competes with beta-catenin/TCF4 for binding to a distal regulatory region of the BMP4 locus that has been previously linked to increased susceptibility to develop CRC. Hence, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation.

Publication Title

The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression.

Sample Metadata Fields

Specimen part, Cell line

View Samples
accession-icon GSE56348
Gene expression microarray profiling in mice hearts with pathological and physiological cardiac hypertrophy
  • organism-icon Mus musculus
  • sample-icon 30 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Compelling evidence suggests that mitochondrial dysfunction contributes to the pathogenesis of heart failure, including defects in the substrate oxidation, and the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS). However, whether such changes occur early in the development of heart failure, and are potentially involved in the pathologic events that lead to cardiac dysfunction is unknown. To address this question, we conducted transcriptomic/metabolomics profiling in hearts of mice with two progressive stages of pressure overload-induced cardiac hypetrophy: i) cardiac hypertrophy with preserved ventricular function achieved via transverse aortic constriction for 4 weeks (TAC) and ii) decompensated cardiac hypertrophy or heart failure (HF) caused by combining 4 wk TAC with a small apical myocardial infarction. Transcriptomic analyses revealed, as shown previously, downregulated expression of genes involved in mitochondrial fatty acid oxidation in both TAC and HF hearts compared to sham-operated control hearts. Surprisingly, however, there were very few changes in expression of genes involved in other mitochondrial energy transduction pathways, ETC, or OXPHOS. Metabolomic analyses demonstrated significant alterations in pathway metabolite levels in HF (but not in TAC), including elevations in acylcarnitines, a subset of amino acids, and the lactate/pyruvate ratio. In contrast, the majority of organic acids were lower than controls. This metabolite profile suggests bottlenecks in the carbon substrate input to the TCA cycle. This transcriptomic/metabolomic profile was markedly different from that of mice PGC-1a/b deficiency in which a global downregulation of genes involved in mitochondrial ETC and OXPHOS was noted. In addition, the transcriptomic/metabolomic signatures of HF differed markedly from that of the exercise-trained mouse heart. We conclude that in contrast to current dogma, alterations in mitochondrial metabolism that occur early in the development of heart failure reflect largely post-transcriptional mechanisms resulting in impedance to substrate flux into the TCA cycle, reflected by alterations in the metabolome.

Publication Title

Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE49104
dDsk2 stabilizes dHP1c binding at TSS
  • organism-icon Drosophila melanogaster
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome 2.0 Array (drosophila2)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes.

Sample Metadata Fields

Cell line

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accession-icon GSE49103
Drosophila ROW RNAi gene expression profiling
  • organism-icon Drosophila melanogaster
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome 2.0 Array (drosophila2)

Description

Heterochromatin-protein 1 (HP1) is a functionally diverse family of proteins. In particular, Drosophila dHP1c forms a complex with the transcription factors WOC and ROW (dHP1EU) that localizes at euchromatin and regulates gene expression.

Publication Title

dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE12378
Integration of ERG gene mapping and gene expression profiling identifies distinct categories of human prostate cancer
  • organism-icon Homo sapiens
  • sample-icon 39 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)

Description

OBJECTIVE: Previous expression microarray analyses have failed to take into consideration the genetic heterogeneity and complex patterns of ERG gene alteration frequently found in cancerous prostates. The objective of this study is for the first time, to integrate the mapping of ERG gene alterations with the collection of expression microarray data.

Publication Title

Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer.

Sample Metadata Fields

Sex, Specimen part

View Samples
accession-icon GSE18737
Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.

Sample Metadata Fields

Specimen part

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accession-icon GSE18669
Analysis of murine hematopoieitic stem cells, multipotent progenitors, PreMegE progenitors and mature CD4+ T cells
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

An investigation of the global gene expression signatures of murine hematopoietic stem cell differentiation during steady state hematopoiesis.

Publication Title

Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE8407
Elucidation of the phenotypic, functional and molecular topography of a myeloerythroid progenitor cell hierarchy
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

The major myeloid blood cell lineages, including erythrocytes, platelets, granulocytes and macrophages, are generated from hematopoietic stem cells (HSC) by differentiation through a series of increasingly more committed progenitor cells. Precise phenotypic identification and functional characterization of such intermediate progenitors has important consequences for understanding fundamental differentiation processes and is clinically relevant since such events become dysregulated in various disease settings, including leukemia. While previous studies have suggested a hierarchy for myeloid differentiation involving a common progenitor through which all myeloid lineages are derived, several recent studies have suggested that such a developmental intermediate might not be an absolute requirement. Here, we evaluated the functional in vitro and in vivo potentials of a range of prospectively isolated myeloid precursors with differential expression of CD150, Endoglin and CD41. Our studies reveal a complex hierarchy of myeloerythroid progenitors with distinct and developmentally restricted lineage potentials. Global gene expression signatures of these cellular subsets revealed expression patterns consistent with their functional capacities, while hierarchical clustering analysis provides details on their lineage relationships. These data challenge existing models of hematopoietic differentiation, by suggesting that progenitors of the innate and adaptive immune system in the adult separate late, and to a large extent, following the divergence of megakaryocytic/erythroid potential.

Publication Title

Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy.

Sample Metadata Fields

No sample metadata fields

View Samples
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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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