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accession-icon SRP093261
Embryonic VHL-HIF signaling defines dynamic heart metabolic compartments essential for cardiac maturation
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer IIx

Description

While gene regulatory networks involved in cardiogenesis have been characterized, the role of bioenergetics remains less studied. Here we show that until midgestation, myocardial metabolism is compartmentalized, with a glycolytic signature restricted to compact myocardium contrasting with increased mitochondrial oxidative activity in the trabeculae. HIF1a regulation mirrors this pattern, with expression predominating in compact myocardium and scarce in trabeculae. By midgestation, the compact myocardium downregulates HIF1a and switches toward oxidative metabolism. Deletion of the E3 ubiquitin ligase Vhl results in HIF1a hyperactivation, disrupting metabolic compartmentalization and blocking the midgestational shift toward oxidative phosphorylation. Moreover, the altered glycolytic signature induced by HIF1 trabecular activation precludes regulation of genes essential for cardiac conduction system establishment. Our findings reveal VHL-HIF-mediated metabolic compartmentalization in the developing heart and the connection between metabolism and myocardial differentiation. These results highlight the importance of bioenergetics in ventricular myocardium specialization and its potential relevance to congenital heart disease. Overall design: RNA was isolated from individual E12.5 embryonic hearts after removal of the atria and valvular region. KOs and control littermates were matched by somite count, and a total number of 3 KOs and 3 controls from 3 independent litters were used. For RNA extraction, QIAzol Lysis Reagent (Qiagen; CA; USA) and the miRNeasy Mini Kit (Qiagen; CA; USA) were used. RNA was quantified and its purity checked with a NanoDrop ND-1000 spectophotometer (Thermo Scientific; MA; USA). RNA integrity was verified with an Agilent 2100 Bioanalyzer (Agilent Technologies; CA; USA). Index-tagged cDNA libraries were constructed from 500 ng of total RNA using the TruSeq RNA Sample Preparation v2 Kit (Illumina; CA; USA). Libraries were quantified by Quant-iTâ„¢ dsDNA HS assay in a Q-bit fluorometer (Life Technologies; CA; USA). Average library size and size distribution were determined by DNA 1000 assay in an Agilent 2100 Bioanalyzer. Libraries were normalized to 10nM using 10mM Tris-HCl, pH8.5 containing 0.1% Tween 20 and then applied to an Illumina flow cell for cluster generation (True Seq SR Cluster Kit V2 cBot) and sequencing-by-synthesis. Single reads of length 75bp were generated with the TruSeq SBS Kit v5 (Illumina; CA; USA) on the Genome Analyzer IIx platform, following the standard RNA sequencing protocol. Reads were further processed using the CASAVA package (Illumina; CA; USA) to split reads according to adapter indexes and produce fastq files.

Publication Title

Myocardial VHL-HIF Signaling Controls an Embryonic Metabolic Switch Essential for Cardiac Maturation.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE24473
Ras-Association Domain Family 1C Protein Promotes Breast Cancer Cell Migration
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells

Publication Title

Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis.

Sample Metadata Fields

Cell line

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accession-icon GSE59232
Control of YAP/TAZ by glucose metabolism
  • organism-icon Homo sapiens
  • sample-icon 38 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

Aerobic glycolysis tunes YAP/TAZ transcriptional activity.

Sample Metadata Fields

Cell line, Treatment

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accession-icon GSE59228
Regulation of gene expression by glucose metabolism in mammary cell lines
  • organism-icon Homo sapiens
  • sample-icon 14 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Reprogramming of cancer cell metabolism toward aerobic glycolysis, i.e. the Warburg effect, is a hallmark of cancer; according to current views, the rationale for selecting such energy-inefficient metabolism is the need to increase cellular biomass to sustain production of daughter cells and proliferation. In this view, metabolic reprogramming is considered as a simple phenotypic endpoint that occurs as a consequence of signal transduction mechanisms, including oncogene-driven nutrient uptake and metabolic rewiring. A newly emerging paradigm is instead that transcriptional networks and oncogenic signaling can also be regulated downstream of metabolic pathways, that assume causative roles in controlling cancer cell behavior, above and beyond their core biochemical function. To explore possible links between glucose metabolism and nuclear gene transcription we compared immortalized mammary epithelial cells (MCF10A) and metastatic breast cancer cells (MDA-MB-231) growing in high glucose or in the presence of a widely used inhibitor of glucose uptake / glucose metabolism, 2-deoxy-glucose (2DG).

Publication Title

Aerobic glycolysis tunes YAP/TAZ transcriptional activity.

Sample Metadata Fields

Cell line, Treatment

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accession-icon GSE59230
Regulation of gene expression by loss-of-YAP/TAZ in MDA-MB-231 breast cancer cells
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

YAP1 (Yes-associated protein 1) and TAZ (transcriptional coactivator with PDZ-binding motif, or WWTR1) are nucleo-cytoplasmic shuttling proteins that can function in the nucleus as transcriptional coactivators. Their role in regulating gene transcription has been so far mainly investigated by overexpressing YAP1 or TAZ, while here we sought to determine which genes are regulated by endogenous levels of YAP/TAZ. To this end, we compared MCF10A cells transfected with a control non-targeting siRNA to cells transfected with two independent mixes of siRNA targeting both YAP and TAZ.

Publication Title

Aerobic glycolysis tunes YAP/TAZ transcriptional activity.

Sample Metadata Fields

Cell line

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accession-icon GSE59229
Regulation of gene expression by loss-of-YAP/TAZ in MCF10A mammary epithelial cells
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

YAP1 (Yes-associated protein 1) and TAZ (transcriptional coactivator with PDZ-binding motif, or WWTR1) are nucleo-cytoplasmic shuttling proteins that can function in the nucleus as transcriptional coactivators. Their role in regulating gene transcription has been so far mainly investigated by overexpressing YAP1 or TAZ, while here we sought to determine which genes are regulated by endogenous levels of YAP/TAZ. To this end, we compared MCF10A cells transfected with a control non-targeting siRNA to cells transfected with two independent mixes of siRNA targeting both YAP and TAZ.

Publication Title

Aerobic glycolysis tunes YAP/TAZ transcriptional activity.

Sample Metadata Fields

Cell line

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accession-icon GSE35823
Expression data from Bovine leukemia virus (BLV) Tax-transfected HeLa cells
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A 2.0 Array (hgu133a2)

Description

Bovine leukemia virus (BLV) Tax is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G) or reduced (TaxS240P) transactivation effects on BLV replication and propagation. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we used a large-scale host cell gene-profiling approach.

Publication Title

Identification of bovine leukemia virus tax function associated with host cell transcription, signaling, stress response and immune response pathway by microarray-based gene expression analysis.

Sample Metadata Fields

Cell line

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accession-icon GSE34750
Expression data from Human Tax transfected HeLa cell
  • organism-icon Homo sapiens
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A 2.0 Array (hgu133a2)

Description

Human T cell leukemia virus type 1 (HTLV-1) Tax is potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. In this study, a large-scale host cell signaling events related to cellular proliferation were used to identify genes involved in Tax-mediated cell signaling events related to cellular proliferation and apoptosis.

Publication Title

Visualizing spatiotemporal dynamics of apoptosis after G1 arrest by human T cell leukemia virus type 1 Tax and insights into gene expression changes using microarray-based gene expression analysis.

Sample Metadata Fields

Cell line

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accession-icon GSE15090
Gene expression profiles in muscle tissue from FSHD patients
  • organism-icon Homo sapiens
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Muscle biopsies from biceps and deltoid were taken from 5 patients with FSHD, 5 asymptomatic carriers and 5 normal controls. The genome-wide expression patterns were compared using Affymetrix U133 Plus 2.0 chips.

Publication Title

Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers.

Sample Metadata Fields

Sex, Age, Specimen part, Disease

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accession-icon GSE24928
Gene expression change induced by bisphenol A in mouse urogenital sinus
  • organism-icon Mus musculus
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Bisphenol A (BPA), an endocrine-disrupting chemical (EDC), is a well-known, ubiquitous estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we first examined the alterations of in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS).

Publication Title

Endocrine disrupter bisphenol A increases in situ estrogen production in the mouse urogenital sinus.

Sample Metadata Fields

Specimen part

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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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