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SRP144088
Mus musculus
8 Downloadable Samples
Illumina HiSeq 4000
Description
Blood-retina barrier (BRB) formation and retinal angiogenesis depend on beta-catenin signaling induced by the ligand norrin (NDP), the receptor frizzled4 (FZD4), co-receptor LRP5, and the tetraspanin TSPAN12. Impaired NDP/FZD4 signaling causes familial exudative vitreoretinopathy (FEVR), which may lead to blindness. Endothelial-cell specific inactivation of the Tspan12 gene at P28 using a Cdh5-CreERT2 driver shows that TSPAN12 functions in ECs to promote vascular morphogenesis and BRB formation in developing mice, and BRB maintenance in adult mice. 12 month after Tspan12 inactivation and loss of BRB maintenance with massive IgG and albumin extravasation we observe complement activation, cystoid edema, and impaired beta-wave in electroretinograms. RNA-Seq 6 month after Tspan12 inactivation provides a detailed view on the transcriptional response, including activation of antibody effector systems (complement and Fc receptors), inflammation and microglia responses, extracellular matrix organization and remodeling, and other responses. Overall design: Endothelial cell-specific inactivation of floxed Tspan12 was induced at P28 using a Cdh5-CreERT2 driver and total retina RNA (ribodepleted) from 4 control or ECKO retinas (8 samples) was subjected to RNA-Seq 6 months later
Publication Title
Endothelial Cell-Specific Inactivation of TSPAN12 (Tetraspanin 12) Reveals Pathological Consequences of Barrier Defects in an Otherwise Intact Vasculature.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Caenorhabditis elegans
- 43 Downloadable Samples
- Illumina HiSeq 2000
Description
Longevity mechanisms increase lifespan by counteracting the effects of aging. However, whether longevity mechanisms counteract the effects of aging continually throughout life, or whether they act during specific periods of life, preventing changes that precede mortality is unclear. Here, we uncover transcriptional drift, a phenomenon that describes how aging causes genes within functional groups to change expression in opposing directions. These changes cause a transcriptome-wide loss in mRNA stoichiometry and loss of co-expression patterns in aging animals, as compared to young adults. Using Caenorhabditis elegans as a model, we show that extending lifespan by inhibiting serotonergic signals by the antidepressant mianserin attenuates transcriptional drift, allowing the preservation of a younger transcriptome into an older age. Our data are consistent with a model in which inhibition of serotonergic signals slows age-dependent physiological decline and the associated rise in mortality levels exclusively in young adults, thereby postponing the onset of major mortality. Overall design: In this study set out to measure aging in the transcriptome by determining drift-variance changes with age in C.elegans. We set up three different cohorts of water or mianserin treated animals. The title of each cohort indicates the treatment (e.g. h2o or mia), the concentration (mia2, mia10, mia50), the day when the treatment was started (e.g. d1= day 1 of adulthood) and the day when the sample was collected (e.g. d10= day 10 of adulthood). cohort #1: Celegans was treated with water or mianserin (50uM) on day 1 and RNA was harvested on day1 (water only), d3, d5 and day 10 (file titles: h2o d1/d1, h2o d1/d3, h2o d1/d5, h2o d1/d10, mia50 d1/d3, mia50 d1/d5, mia50 d1/d10) cohort #2: Celegans was treated with mianserin (50uM) starting on day 3, and day 5, RNA was harvested on day 5 or 10 (file titles: mia50 d3/d10, mia50 d5/d10, mia50 d3/d5) cohort #3: Celegans was treated with mianserin 2 uM and 10 uM Mianserin on day 1 and Rna harvested on day 5 (file titles: mia2 d1/d5, mia10 d1/d5)
Publication Title
Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality.
Sample Metadata Fields
Subject
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Yeast grown in synthetic complete medium (SD) until glucose depletion is aged chronologically. Cells are stressed by lacking of nutrients and accumulating toxic substances, and thus undergo gene expression changes in response to those.
Publication Title
Genome-wide expression analyses of the stationary phase model of ageing in yeast.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The protein secretory pathway must maintain homoeostasis while producing a wide assortment of proteins in different conditions. It is also used extensively to produce many useful proteins in biotechnology. As such, secretory pathway dysfunction can be highly detrimental to the cell, resulting in the molecular basis for many human diseases, and can drastically inhibit product titers in biochemical production. Because the secretory pathway is a highly-integrated, multi-organelle system, dysfunction can happen at many levels and dissecting the root cause can be challenging.
Publication Title
Imbalance of heterologous protein folding and disulfide bond formation rates yields runaway oxidative stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
In this study we focus on two Saccharomyces cerevisiae strains with varying production of heterologous -amylase and we compare the metabolic fluxes and transcriptional regulation at aerobic and anaerobic conditions, in particular with the objective to identify the final electron acceptor for protein folding.
Publication Title
Anaerobic α-amylase production and secretion with fumarate as the final electron acceptor in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
In this study we focus on two Saccharomyces cerevisiae (CEN. PK series) strains producing either insulin precursor or amylase and we compare the transcriptional regulation at different dilution rates, in particular with the objective to identify the relationship between cell metabolism and recombinant protein production.
Publication Title
Correlation of cell growth and heterologous protein production by Saccharomyces cerevisiae.
Sample Metadata Fields
Treatment
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Alzheimers disease (AD) is a progressive neurodegenerative disorder. Oligomers of Amyloid- peptides (A) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of A associated with AD are A40 and A42, the latter being more prone to form oligomers and toxic. Humanized yeast models are currently applied to unravel the cellular mechanisms behind A toxicity. Here, we took a systems biology approach to study two yeast AD models which expressed either A40 or A42 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 A42, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondrial functionality and ATP generation in A42 expressing cells, which matched with observed aberrant fragmented mitochondrial structures. Genome-wide expression levels analysis showed that A42 expression triggers strong ER stress and unfolded protein responses (UPR). Expression of A40 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 A 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
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
In the yeast Saccharomyces cerevisiae, accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein response (UPR) mediated by Hac1p, whereas the heat shock response (HSR) mediated by Hsf1p mainly regulates cytosolic processes and protects the cell from different stresses. In this study, we find that a constitutive activation of the HSR by over-expression of a mutant HSF1 gene could relieve ER stress in both wild type and hac1 UPR-deficient cells.
Publication Title
Management of the endoplasmic reticulum stress by activation of the heat shock response in yeast.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 12 Downloadable Samples
- Affymetrix Chicken Gene 1.1 ST Array (chigene11st)
Description
White Striping and Wooden Breast (WS/WB) are abnormalities increasingly occurring in the fillets of high breast yield and growth rate chicken hybrids. These defects lead to consistent economic losses for poultry meat industry, as affected broilers fillets present an impaired visual appearance that negatively affects consumers acceptability. Previous studies have highlighted in affected fillets a deeply damaged muscle, showing profound inflammation, fibrosis and lipidosis. The present study investigated the differentially expressed genes and pathways linked to the compositional changes observed in WS/WB breast muscles, in order to outline a more complete framework of the gene networks related to the occurrence of this complex pathological picture. The biochemical composition was performed on 20 Pectoralis major samples obtained from high breast yield and growth rate broilers (10 affected vs. 10 normal) and 12 out of the 20 samples were used for the microarray gene expression profiling (6 affected vs. 6 normal). The obtained results indicate strong changes in muscle mineral composition, coupled to an increased deposition of fat. In addition, 204 differentially expressed genes (DEG) were found: 102 up-regulated and 102 down-regulated in affected breasts. The gene expression pathways found more altered in WS/WB muscles are those related to muscle development, polysaccharide metabolic processes, proteoglycans synthesis, inflammation and calcium signaling pathway. On the whole, the findings suggest that a multifactorial and complex etiology is associated with the occurrence of WS/WB muscle abnormalities, contributing to further define the transcription patterns associated to these myopathies.
Publication Title
Detection of differentially expressed genes in broiler pectoralis major muscle affected by White Striping - Wooden Breast myopathies.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina HiSeq 2000
Description
Overall goal: To identify genes that will cause non-fusogenic fibroblasts to become fusogenic. Purpose of analysis: To generate transcriptional profile of non-fusogenic fibroblasts, using 10T1/2 fibroblasts transduced with empty retrovirus as model. Experimental structure: The profile generated from the RNAseq analysis would be compared with transcriptional profile of MyoD-expressing fibroblasts (GEO DataSet GSE34907) to identify genes regulating fusion in muscle cells. Overall design: RNAseq analysis of total RNA from 10T1/2 fibroblasts transduced with retrovirus carrying empty pBabe-X retroviral vector was carried out to generate a transcriptional profile of a model of non-fusogenic fibroblasts.
Publication Title
Myomerger induces fusion of non-fusogenic cells and is required for skeletal muscle development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples