Filters
Technology
Platform
SRP098713
Homo sapiens
6 Downloadable Samples
Illumina HiSeq 2500
Description
The accumulation of irreparable cellular damage restricts healthy lifespan after acute stress or natural aging. Senescent cells are thought to impair tissue function and their genetic clearance can successfully delay features of aging. Identifying how senescent cells avoid apoptosis would allow for the prospective design of anti-senescence compounds to address whether homeostasis can be restored. Here, we identify FOXO4 as a pivot in the maintenance of senescent cell viability. We designed a FOXO4-based peptide which selectively competes for interaction of FOXO4 with p53. In senescent cells, this results in p53 nuclear exclusion and cell-intrinsic apoptosis. Importantly, under conditions where it was well tolerated, the FOXO4 peptide restored liver function after Doxorubicin-induced chemotoxicity. Moreover, in fast aging XpdTTD/TTD, as well as in naturally aged mice the FOXO4 peptide could counteract the loss of fitness, fur density and renal function. Thus, it is possible to therapeutically target senescent cells and thereby effectively counteract senescence-associated loss of tissue homeostasis. Overall design: mRNA expression levels are compared between IR-induced senescent and proliferating IMR90 cells in triplicate
Publication Title
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Effect of absence of interaction with MHC class II on memory CD4 T cells
Publication Title
Noncognate interaction with MHC class II molecules is essential for maintenance of T cell metabolism to establish optimal memory CD4 T cell function.
Sample Metadata Fields
Sex, Specimen part
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Nitric oxide and NO-derived species (RNS) are defense molecules with broad antimicrobial activity. Micro-organisms have developed strategies to sense RNS and counteract their damaging effects. We used Saccharomyces cerevisiae, harbouring a deletion of YHB1 that encodes the main NO scavenger enzyme, to study consequences of RNS exposure on whole genome transcriptional response. The expression of >700 genes was altered on RNS treatment. No major role for ROS-scavenging enzymes was found, and the respiratory chain, the main site of ROS production, had only minor involvement in the RNS-induced stress. The changes were generally transient and also found after treatment with the respiratory inhibitor myxothiazol. 117 genes however showed a persistent response which was not observed after myxothiazol treatment. Of these, genes of the glutathione and DNA repair systems, iron homeostasis and transport were found up-regulated. Severe repression of genes of respiratory chain enzymes was observed. Many of these genes are known to be regulated by the transcription factor Hap1p suggesting that RNS might interfere with Hap1p activity. We showed also that Msn2/4p and Yap1p, key regulators of the response to, respectively, general stress and oxidative stress, played a role in mediating the RNS-induced response.
Publication Title
Transcriptional response to nitrosative stress in Saccharomyces cerevisiae.
Sample Metadata Fields
Compound, Time
View Samples- Saccharomyces cerevisiae
- 29 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The mitochondrial respiratory chain is composed of lipoprotein complexes imbedded in the inner mitochondrial membrane. This chain of enzymes transfers electrons from NADH and FADH2, provided from divers metabolic pathways, to oxygen. It couples the transfer of electrons to the translocation of protons across the membrane. Several clinical syndromes have been associated with respiratory dysfunction caused by mitochondrial or nuclear mutations. A number of mutations in the mitochondrial genes encoding for cytochrome b (CYTB) and cytochrome oxidase (COX 1, 2 and 3) have been linked with diseases. We are using yeast mutants to characterize the deleterious effect of mutations reported in patients on the assembly and catalytic properties of the affected enzymes, and to study the impact of mutations in nuclear genes, such as OXA1, encoding for factors required for the assembly of the respiratory complexes. In this work, we monitored the effects of the mutations causing respiratory defect on the whole genome expression. We compared the change in gene expression in rho0 cells (with a complete deletion of the mitochondrial genome, and by consequence without respiratory chain), in cells with either a single defective enzyme or several, and in cells after prolonged treatment with the bc1 inhibitors myxothiazol or antimycin. The impact of the mutations on the respiratory function ranged from mild to severe. The expression of approx. 350 genes was changed in at least one mutant. Cluster analysis was performed using the Cluster program (Eisen, 1998, PNAS 95:14863). Four groups of genes were studied in more details: Group A, the most repressed genes; Group B, the most over-expressed genes; Group C, genes more repressed in rho0 and Doxa1 cells; and Group D, genes more over-expressed in Doxa1.
Publication Title
Multiple defects in the respiratory chain lead to the repression of genes encoding components of the respiratory chain and TCA cycle enzymes.
Sample Metadata Fields
Compound
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
RNA helicases DDX5 and DDX17 are members of a large family of highly conserved proteins involved in gene expression regulation, although their in vivo targets and activities in biological processes like cell differentiation, that requires reprogramming of gene expression programs at multiple levels, are not well characterized. In this report, we uncovered a new mechanism by which DDX5 and DDX17 cooperate with hnRNP H/F splicing factors to define epithelial- and myoblast-specific splicing subprograms. We next observed that downregulation of DDX5 and DDX17 protein expression during epithelial to mesenchymal transdifferentiation and during myogenesis contributes to switching splicing programs during these processes. Remarkably, this downregulation is mediated by the production of microRNAs induced upon differentiation in a DDX5/DDX17-dependent manner. Since DDX5 and DDX17 also function as coregulators of master transcriptional regulators of differentiation, we propose to name these proteins master orchestrators of differentiation, that dynamically orchestrate several layers of gene expression.
Publication Title
RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and splicing programs in cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transgenic mice were generated that expressed the inhibitor of apoptosis and mitotic regulator survivin in pancreatic islet beta cells. Control non-transgenic or transgenic islets were then used in a model of islet transplantation in diabetic recipient mice and tested for their ability to correct hyperglycemia and allow long-term engraftment of tranplanted islets in vivo. Control or transgenic islets were analyzed by chip microarray for potential transcriptional changes associated with transgenic expression of survivin, in vivo.
Publication Title
Genome-wide analysis of Polycomb targets in Drosophila melanogaster.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In order to investigate the impact of MMP-14 (MT1-MMP) and three-dimensional (3D) culture conditions on the transcriptomes of a human breast adenocarcinoma cell line, we performed a microarray analysis from RNAs isolated from MCF-7 cells expressing either an empty vector (CTRL) or human MMP-14 cDNA (MT1) in monolayer (2D) and 3D collagen (3D Col) growth conditions.
Publication Title
A membrane-type-1 matrix metalloproteinase (MT1-MMP)-discoidin domain receptor 1 axis regulates collagen-induced apoptosis in breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters (DTPs) that is dynamically maintained within a wide variety of tumor cell populations. Here, we explored a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs revealed miR-371-3p as a potent suppressor of drug tolerance. PRDX6 (peroxiredoxin 6) was identified as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKC activity and reactive oxygen species. PRDX6 expression is associated with poor prognosis in cancers of multiple tissue origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest that co-targeting of PRDX6 or modulating miR-371-3p expression together with targeted cancer therapies may delay or prevent acquired drug resistance.
Publication Title
Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Influence of ovarian stimulation with 200 IU of hCG, (administered in the late follicular phase among ICSI patients undergoing a GnRH-antagonist protocol), on the endometrium on the day of oocyte pick-up.
Publication Title
Gene expression profile in the endometrium on the day of oocyte retrieval after ovarian stimulation with low-dose hCG in the follicular phase.
Sample Metadata Fields
Specimen part, Treatment
View Samples