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GSE93864
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarrays to investigate differential gene expression in different thyroid hormone receptor beta mouse models. Hypothyroid wild type, TRbeta KO and TRbeta GS mutant mice were treated with T3 or vehicle alone. Microarray analysis revealed that the gene expression pattern in TRbeta GS mutant mice was similar to that in TRbeta KO mice.
Publication Title
Noncanonical thyroid hormone signaling mediates cardiometabolic effects in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Normal cells require continuous exposure to growth factors, in order to cross a restriction point and commit to cell cycle progression. This can be replaced by two short, appropriately spaced pulses of growth factors, where the first pulse primes a process, which is completed by the second pulse, and enables restriction point crossing. Through integration of comprehensive proteomic and transcriptomic analyses of each pulse, we identified three processes that regulate restriction point crossing: (i) The first pulse induces essential metabolic enzymes and activates p53-dependent restraining processes. (ii) The second pulse eliminates, via the PI3K/AKT pathway, the suppressive action of p53, as well as (iii) sets an ERK-EGR1 threshold mechanism, which digitizes graded external signals into an all-or-none decision obligatory for S-phase entry. Together, our findings uncover novel gating mechanisms, which ensure that cells ignore fortuitous growth factors, and undergo proliferation only in response to consistent mitogenic signals.
Publication Title
Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Cancer cells that express oncogenic alleles of RAS typically require sustained expression of the mutant allele for survival, but the molecular basis of this oncogene dependency remains incompletely understood. To identify genes that can functionally substitute for oncogenic RAS, we systematically expressed 15,294 open reading frames in a human KRAS-dependent colon cancer cell line engineered to express an inducible KRAS-specific shRNA. We found 147 genes that promoted survival in the setting of KRAS suppression. In this model, the transcriptional co-activator YAP1 rescued cell viability in KRAS-dependent cells upon suppression of KRAS and was required for KRAS-induced cell transformation. Acquired resistance to Kras suppression in a Kras-driven murine lung cancer model also involved increased YAP1 signaling. KRAS and YAP1 converge on the transcription factor FOS and activate a transcriptional program involved in regulating the epithelial-mesenchymal transition (EMT). Together, these findings implicate transcriptional regulation of EMT by YAP1 as a significant component of oncogenic RAS signaling.
Publication Title
KRAS and YAP1 converge to regulate EMT and tumor survival.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
Illumina HiSeq 2000
Description
Cancer cells that express oncogenic alleles of RAS typically require sustained expression of the mutant allele for survival, but the molecular basis of this oncogene dependency remains incompletely understood. To identify genes that can functionally substitute for oncogenic RAS, we systematically expressed 15,294 open reading frames in a human KRAS-dependent colon cancer cell line engineered to express an inducible KRAS-specific shRNA. We found 147 genes that promoted survival in the setting of KRAS suppression. In this model, the transcriptional co-activator YAP1 rescued cell viability in KRAS-dependent cells upon suppression of KRAS and was required for KRAS-induced cell transformation. Acquired resistance to Kras suppression in a Kras-driven murine lung cancer model also involved increased YAP1 signaling. KRAS and YAP1 converge on the transcription factor FOS and activate a transcriptional program involved in regulating the epithelial-mesenchymal transition (EMT). Together, these findings implicate transcriptional regulation of EMT by YAP1 as a significant component of oncogenic RAS signaling Overall design: Three biological replicates of primary lung adenocarcinoma cells derived from the Kras Lox-STOP-Lox-G12D;p53flox/flox (KP) mouse lung cancer model into which a doxycycline-inducible shRNA targeting Kras expressed from the 3’UTR of GFP was introduced (KP-KrasA cells) were analyzed at timepoints (days) D0, D4, and D21.
Publication Title
KRAS and YAP1 converge to regulate EMT and tumor survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 216 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Many studies have addressed the effects of adult diet on gene expression in Drosophila melanogaster, however, little is known about how developmental diet influences adult gene expression, and how this interacts with adult dietary conditions.
Publication Title
Relating past and present diet to phenotypic and transcriptomic variation in the fruit fly.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 115 Downloadable Samples
- Illumina HiSeq 2500
Description
The study aims to determine the set of transcriptional cell types that make up the mouse brain
Publication Title
Molecular Architecture of the Mouse Nervous System.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ensuring cooperation among formerly autonomous cells has been a central challenge in the evolution of multicellular organisms. One solution is monoclonality, but this option does not eliminate genetic and epigenetic variability, leaving room for exploitative behavior. We therefore hypothesized that embryonic development must be protected by robust regulatory mechanisms that prevent aberrant clones from superseding wild-type cells. Using a genome-wide screen in murine induced pluripotent stem cells, we identified a network of genes (centered on p53, topoisomerase 1, and olfactory receptors) whose downregulation caused the cells to replace wild-type cells, both in vitro and in the mouse embryowithout perturbing normal development. These genes thus appear to fulfill an unexpected role in fostering cell cooperation.
Publication Title
Safeguards for cell cooperation in mouse embryogenesis shown by genome-wide cheater screen.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 46 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown.
Publication Title
Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension.
Sample Metadata Fields
Sex, Specimen part
View Samples- Saccharomyces cerevisiae
- 11 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The present study aims to explore the role of Rim15 in both physiology and genome wide expression in S. cerevisiae under severe caloric restriction. Non-growing but metabolically active cultures of S. cerevisiae are of major interest for application in industry and as model systems for aging in higher eukaryotes. Using retentostat cultivations, almost non-growing but metabolic active cultures can be obtained resulting from the severe caloric restriction, yet not starvation, yeast experiences. Rim15 plays an important role in several nutrient sensing pathways and is involved in activating stress response and glycogen accumulation upon nutrient shortage. To investigate the role of Rim15 in the extreme robustness and glycogen accumulation of anaerobic retentostat cultures, a rim15 deletion strain is compared with its parental strain under anaerobic calorie restriction on both physiology and transcriptome.
Publication Title
To divide or not to divide: a key role of Rim15 in calorie-restricted yeast cultures.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 747 Downloadable Samples
- Illumina HiSeq 2000
Description
Heterogeneous pools of adult neural stem cells (NSCs) contribute to brain maintenance and regeneration after injury. The balance of NSC activation and quiescence, as well as the induction of lineage-specific transcription factors, may contribute to diversity of neuronal and glial fates. To identify molecular hallmarks governing these characteristics, we performed single-cell sequencing of an unbiased pool of adult subventricular zone NSCs. This analysis identified a discrete, dormant NSC subpopulation that already expresses distinct combinations of lineage-specific transcription factors during homeostasis. Dormant NSCs enter a primed-quiescent state before activation, which is accompanied by downregulation of glycolytic metabolism, Notch, and BMP signaling and a concomitant upregulation of lineage-specific transcription factors and protein synthesis. In response to brain ischemia, interferon gamma signaling induces dormant NSC subpopulations to enter the primed-quiescent state. This study unveils general principles underlying NSC activation and lineage priming and opens potential avenues for regenerative medicine in the brain. Overall design: Single cell RNAseq of cells isolated from their in vivo niche in the subventricular zone, Striatum and Cortex during homeostasis as well as following ischemic injury. In total 272 single cells. (<WT>: homeostasis samples; <Ischemic_injured> and <Ischemic_injured_and_Interferon_gamma_knockout>: samples following ischemic injuried).
Publication Title
Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury.
Sample Metadata Fields
No sample metadata fields
View Samples