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GSE18157
Caenorhabditis elegans, Saccharomyces cerevisiae, Rattus norvegicus
17 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Biotin is cofactor of crucial enzymes for intermediary metabolism, and its deficiency affects the transcription of some critical genes of mammalian glucose metabolism. However, the precise mechanisms of biotin starvation on gene expression are unknown. Here we show that metabolic changes ushered by deficiency of this vitamin sets in motion extensive reorganization of carbon metabolism gene expression, consistent across three diverse eukaryotes, that is mediated through a regulatory circuitry at the genome level similar in the three species.
Publication Title
Biotin starvation with adequate glucose provision causes paradoxical changes in fuel metabolism gene expression similar in rat (Rattus norvegicus), nematode (Caenorhabditis elegans) and yeast (Saccharomyces cerevisiae).
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus, Homo sapiens
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
Illumina Genome Analyzer II
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia.
Sample Metadata Fields
Disease, Cell line
View Samples- Rattus norvegicus
- 54 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Molecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia and might contribute to its pathogenesis, we determined global gene expression profiles in muscles of rats aged 6, 12, 18, 21, 24, and 27 months. These rats exhibit sarcopenia beginning at 21 months. Correlation of the gene expression versus muscle mass or age changes, and functional annotation analysis identified gene signatures of sarcopenia distinct from gene signatures of aging. Specifically, mitochondrial energy metabolism (e.g., tricarboxylic acid cycle and oxidative phosphorylation) pathway genes were the most downregulated and most significantly correlated with sarcopenia. Also, perturbed were genes/pathways associated with neuromuscular junction patency (providing molecular evidence of sarcopenia-related functional denervation and neuromuscular junction remodeling), protein degradation, and inflammation. Proteomic analysis of samples at 6, 18, and 27 months confirmed the depletion of mitochondrial energy metabolism proteins and neuromuscular junction proteins. Together, these findings suggest that therapeutic approaches that simultaneously stimulate mitochondrogenesis and reduce muscle proteolysis and inflammation have potential for treating sarcopenia.
Publication Title
Genomic and proteomic profiling reveals reduced mitochondrial function and disruption of the neuromuscular junction driving rat sarcopenia.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
Illumina Genome Analyzer II
Description
The oncogenic transcription factor TAL1/SCL is aberrantly overexpressed in over 40% of cases of T-cell acute lymphoblastic leukemia (T-ALL), emphasizing the importance of the TAL1-regulated transcriptional program in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, GATA3, ETS1 and RUNX1 in T-ALL cells. We find that TAL1 forms an interconnected auto-regulatory loop with its partners, which contributes to the sustained upregulation of its direct target genes. Importantly, we also find the MYB oncogenic transcription factor is directly activated by the TAL1 complex and positively regulates many of the same target genes, thus forming a feed-forward positive regulatory loop that further promotes the TAL1-regulated oncogenic program.
Publication Title
Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their non-transformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, even these genes are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.
Publication Title
HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The retinal pigment epithelium (RPE) provides vital support to photoreceptor cells and its dysfunction is associated with the onset and progression of age-related macular degeneration (AMD). Surgical provision of RPE cells may ameliorate AMD and thus it would be valuable to develop sources of patient-matched RPE cells for this application of regenerative medicine. We describe here the generation of functional RPE-like cells from fibroblasts that represent an important step toward that goal. We identified candidate master transcriptional regulators of RPEs using a novel computational method and then used these regulators to guide exploration of the transcriptional regulatory circuitry of RPE cells and to reprogram human fibroblasts into RPE-like cells. The RPE-like cells share key features with RPEs derived from healthy individuals, including morphology, gene expression and function, and thus represent a step toward the goal of generating patient-matched RPE cells for treatment of macular degeneration.
Publication Title
A Systematic Approach to Identify Candidate Transcription Factors that Control Cell Identity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Msx1 Homeoprotein Recruits Polycomb to the Nuclear Periphery during Development.
Sample Metadata Fields
Specimen part, Cell line
View Samples