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GSE63188
Mus musculus
10 Downloadable Samples
Description
EphB receptors regulate the proliferation and positioning of intestinal stem and progenitor cells. In addition, they can act as tumor promoters for adenoma development, but suppress progression to invasive carcinoma. Here we used imatinib to abrogate Abl kinase activity in ApcMin/+ mice and in mice with LGR5+ stem cells genetically targeted for APC. This treatment inhibited the tumor-promoting effects of EphB signaling without attenuating EphB-mediated tumor suppression, demonstrating the role of EphB signaling in intestinal tumor initiation. The investigated treatment regimen extended the lifespan of ApcMin/+ mice, and reduced cell proliferation in cultured slices of adenomas from FAP patients. These findings connect the EphB signaling pathway to the regulation of intestinal adenoma initiation via Abl kinase. Our findings may have clinical implications for pharmacological therapy against adenoma formation and cancer progression in patients predisposed to develop colon cancer.
Publication Title
An EphB-Abl signaling pathway is associated with intestinal tumor initiation and growth.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
Description
In this dataset, we include the expression data obtained from KRas expressing tumors, matched Kras expressing tumor spheres, surviving cells and surviving cells after KRas re-expression for 24hs
Publication Title
Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 5 Downloadable Samples
Description
Retinoic acid (RA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin activate distinct ligand-dependent transcription factors, and both cause cardiac malformation and heart failure in zebrafish embryos. We hypothesized that they cause this response by hyperactivating a common set of genes critical for heart development. To test this, we used microarrays to measure transcripts changes in hearts isolated from zebrafish embryos 1,2,4 and 12 h after exposure to 1M RA. We used hierarchical clustering to compare the transcriptional responses produced in the embryonic heart by RA and TCDD. We could identify no early responses in common between the two agents. However, at 12 h both treatments produced a dramatic downregulation of a common cluster of cell cycle progression genes, which we term the Cell Cycle Gene Cluster (CCGC). This was associated with a halt in heart growth. These results suggest that RA and TCDD ultimately trigger a common transcriptional response associated with heart failure, but not through the direct activation of a common set of genes. Among the genes rapidly induced by RA was Nr2F5, a member of the COUP-TF family of transcription repressors. We found that induction of Nr2F5 was both necessary and sufficient for the cardiotoxic response to RA.
Publication Title
Comparative genomics identifies genes mediating cardiotoxicity in the embryonic zebrafish heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 2 Downloadable Samples
Description
The purpose of this experiment is to understand which transcripts are differentially expressed following exposure to TCDD.
Publication Title
TCDD inhibits heart regeneration in adult zebrafish.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 33 Downloadable Samples
Description
Interaction of hematopoietic progenitors with the thymic stromal microenvironment induces them to proliferate, adopt the T cell fate, and asymmetrically diverge into multiple T lineages. Progenitors at various developmental stages are stratified among different regions of the thymus, implying that the corresponding microenvironments differ from one another, and provide unique sets of signals to progenitors migrating between them. The nature of these differences remains undefined. Here we use novel physical and computational approaches to characterize these stromal subregions, distinguishing gene expression in microdissected tissues from that of their lymphoid constituents. Using this approach, we comprehensively map gene expression in functionally distinct stromal microenvironments, and identify clusters of genes that define each region. Quite unexpectedly, we find that the central cortex lacks distinctive features of its own, and instead appears to function by sequestering unique microenvironments found at the cortical extremities, and modulating the relative proximity of progenitors moving between them.
Publication Title
Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Oligomers of Amyloid-β peptides (Aβ) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of Aβ associated with AD are Aβ40 and Aβ42, the latter being more prone to form oligomers and toxic. Humanized yeast models are currently applied to unravel the cellular mechanisms behind Aβ toxicity. Here, we took a systems biology approach to study two yeast AD models which expressed either Aβ40 or Aβ42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected the chronological lifespan and reduced confounding effects of variations during cell growth. Reduced growth rates and biomass yields were observed upon expression of Aβ42, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondrial functionality and ATP generation in Aβ42 expressing cells, which matched with observed aberrant fragmented mitochondrial structures. Genome-wide expression levels analysis showed that Aβ42 expression triggers strong ER stress and unfolded protein responses (UPR). Expression of Aβ40 induced only mild ER stress, leading to activation of UPR target genes that cope with misfolded proteins, which resulted in hardly affected physiology. The combination of well-controlled cultures and AD yeast models strengthen our understanding of how cells translate different levels of Aβ toxicity signals into particular cell fate programs, and further enhance their role as a discovery platform to identify potential therapies.
Publication Title
Interplay of Energetics and ER Stress Exacerbates Alzheimer's Amyloid-β (Aβ) Toxicity in Yeast.
Sample Metadata Fields
Genetic information
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Oligomers of Amyloid-β peptides (Aβ) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of Aβ associated with AD are Aβ40 and Aβ42, the latter being more prone to form oligomers and toxic. Humanized yeast models are currently applied to unravel the cellular mechanisms behind Aβ toxicity. Here, we took a systems biology approach to study two yeast AD models which expressed either Aβ40 or Aβ42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected the chronological lifespan and reduced confounding effects of variations during cell growth. Reduced growth rates and biomass yields were observed upon expression of Aβ42, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondrial functionality and ATP generation in Aβ42 expressing cells, which matched with observed aberrant fragmented mitochondrial structures. Genome-wide expression levels analysis showed that Aβ42 expression triggers strong ER stress and unfolded protein responses (UPR). Expression of Aβ40 induced only mild ER stress, leading to activation of UPR target genes that cope with misfolded proteins, which resulted in hardly affected physiology. The combination of well-controlled cultures and AD yeast models strengthen our understanding of how cells translate different levels of Aβ toxicity signals into particular cell fate programs, and further enhance their role as a discovery platform to identify potential therapies.
Publication Title
Interplay of Energetics and ER Stress Exacerbates Alzheimer's Amyloid-β (Aβ) Toxicity in Yeast.
Sample Metadata Fields
Genetic information
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Oligomers of Amyloid-β peptides (Aβ) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of Aβ associated with AD are Aβ40 and Aβ42, the latter being more prone to form oligomers and toxic. Humanized yeast models are currently applied to unravel the cellular mechanisms behind Aβ toxicity. Here, we took a systems biology approach to study two yeast AD models which expressed either Aβ40 or Aβ42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected the chronological lifespan and reduced confounding effects of variations during cell growth. Reduced growth rates and biomass yields were observed upon expression of Aβ42, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondrial functionality and ATP generation in Aβ42 expressing cells, which matched with observed aberrant fragmented mitochondrial structures. Genome-wide expression levels analysis showed that Aβ42 expression triggers strong ER stress and unfolded protein responses (UPR). Expression of Aβ40 induced only mild ER stress, leading to activation of UPR target genes that cope with misfolded proteins, which resulted in hardly affected physiology. The combination of well-controlled cultures and AD yeast models strengthen our understanding of how cells translate different levels of Aβ toxicity signals into particular cell fate programs, and further enhance their role as a discovery platform to identify potential therapies.
Publication Title
Interplay of Energetics and ER Stress Exacerbates Alzheimer's Amyloid-β (Aβ) Toxicity in Yeast.
Sample Metadata Fields
Genetic information
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Oligomers of Amyloid-β peptides (Aβ) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of Aβ associated with AD are Aβ40 and Aβ42, the latter being more prone to form oligomers and toxic. Humanized yeast models are currently applied to unravel the cellular mechanisms behind Aβ toxicity. Here, we took a systems biology approach to study two yeast AD models which expressed either Aβ40 or Aβ42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected the chronological lifespan and reduced confounding effects of variations during cell growth. Reduced growth rates and biomass yields were observed upon expression of Aβ42, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondrial functionality and ATP generation in Aβ42 expressing cells, which matched with observed aberrant fragmented mitochondrial structures. Genome-wide expression levels analysis showed that Aβ42 expression triggers strong ER stress and unfolded protein responses (UPR). Expression of Aβ40 induced only mild ER stress, leading to activation of UPR target genes that cope with misfolded proteins, which resulted in hardly affected physiology. The combination of well-controlled cultures and AD yeast models strengthen our understanding of how cells translate different levels of Aβ toxicity signals into particular cell fate programs, and further enhance their role as a discovery platform to identify potential therapies.
Publication Title
Interplay of Energetics and ER Stress Exacerbates Alzheimer's Amyloid-β (Aβ) Toxicity in Yeast.
Sample Metadata Fields
Genetic information
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Oligomers of Amyloid-β peptides (Aβ) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of Aβ associated with AD are Aβ40 and Aβ42, the latter being more prone to form oligomers and toxic. Humanized yeast models are currently applied to unravel the cellular mechanisms behind Aβ toxicity. Here, we took a systems biology approach to study two yeast AD models which expressed either Aβ40 or Aβ42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected the chronological lifespan and reduced confounding effects of variations during cell growth. Reduced growth rates and biomass yields were observed upon expression of Aβ42, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondrial functionality and ATP generation in Aβ42 expressing cells, which matched with observed aberrant fragmented mitochondrial structures. Genome-wide expression levels analysis showed that Aβ42 expression triggers strong ER stress and unfolded protein responses (UPR). Expression of Aβ40 induced only mild ER stress, leading to activation of UPR target genes that cope with misfolded proteins, which resulted in hardly affected physiology. The combination of well-controlled cultures and AD yeast models strengthen our understanding of how cells translate different levels of Aβ toxicity signals into particular cell fate programs, and further enhance their role as a discovery platform to identify potential therapies.
Publication Title
Interplay of Energetics and ER Stress Exacerbates Alzheimer's Amyloid-β (Aβ) Toxicity in Yeast.
Sample Metadata Fields
Genetic information
View Samples