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SRP070204
Caenorhabditis elegans
53 Downloadable Samples
Illumina HiSeq 2000
Description
The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins TRX-2 and TRX-3 do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, SKN-1 transcriptional activity remains largely unaffected. Interestingly, RNA-Seq revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport and localization being most prevalent. However, one prominent lipase-related gene, lips-6, is highly up regulated upon loss of trx-1 in a skn-1-dependent manner. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. Overall design: Four samples were analyzed: Two nematode strains were analyzed, each under non-stressed and stressed (10mM NaAs) conditions
Publication Title
TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans.
Sample Metadata Fields
Disease, Cell line, Subject
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
- NextSeq 500
Description
We profiled how animals RNA expression changes in response to osmotic stress, how lin-45 mutants have an altered response to osmotic stress, and how maternal preconditioning at 300 mM NaCl modifies progeny response to 500 mM NaCl Overall design: Examination of total RNAseq at 50 mM NaCl, 500 mM NaCl, and 500 mM NaCl from maternally preconditioned animals
Publication Title
Insulin-like signalling to the maternal germline controls progeny response to osmotic stress.
Sample Metadata Fields
Subject, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mrhl is a non coding RNA identified from mouse chromosome 8. It is a 2.4kb poly adenylated, nuclear restricted RNA expressed in multiple tissues. The 2.4 kb RNA also undergoes a nuclear processing event mediated through Drosha that generates an 80nt intermediate RNA. This study was aimed at understanding the functiion of mrhl by silencing the mrhl RNA in the mouse spermatogonial cells using a pool of siRNAs targeted against the mrhl and analyse the global gene expression change using Affymetrix mouse expression array. The mRNAs that showed significant change in expression in mrhl siRNA treated cells against control were studied further for their biological significance with respect to mrhl silencing.
Publication Title
mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its protein partner Ddx5/p68 in mouse spermatogonial cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 28 Downloadable Samples
- Illumina HiSeq 2500
Description
To determine the role of the cytokine activin A in the regulation of human T follicular helper (Tfh) cell gene program, we performed a transcriptomic analysis (RNA-seq) of human naïve CD4 T cells differentiated in vitro with activin A. The analysis of the gene expression profile driven by activin A, alone or in combination with IL-12 (a know regulator of human Tfh differentiation/function), revealed that activin A can regulate the expression of multiple molecules involved in the differentiation and/or function of human Tfh cells. Overall design: Human naïve CD4 T cells were isolated from fresh PBMCs of healthy control subjects by magnetic bead isolation. Purity was measured by FACS as percentage of CD4+CD45RA+ cells and was 95% or higher. Upon isolation, naïve CD4 T cells were stimulated with anti-CD3/CD28 coated beads in the presence of the following cytokine combinations: no exogenous cytokines (beads only), activin A, IL-12, activin A+IL-12, TGFb, TGFb +IL12. Following 5 days of in vitro culture, live CD4 T cells were FACS sorted and gene expression was analyzed by RNA-seq. Data are from independent donors.
Publication Title
Activin A programs the differentiation of human TFH cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase inhibitor lonafarnib and the tyrosine kinase inhibitor nilotinib. This results in an initial large reduction in cell viability of the culture and inhibition of cell proliferation. However, after a number of days, cell death ceases and the culture becomes drug-tolerant, enabling cell division to resume. We used gene expression profiling to analyze changes in the transcriptome of these leukemia cells over a 3-4 week period, taking samples at the start, the point at which most of the leukemia cells had been eradicated while a small percentage survived, and at the end when the cells were proliferating again.
Publication Title
Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Primary pre-B acute lymphoblastic (ALL) cells do not proliferate long-term ex vivo without the presence of stromal support. We developed and use an ex vivo co-culture model, consisting of mouse leukemic pre-B Bcr/Abl-expressing ALL cells grown with mitotically inactivated mouse embryonic fibroblasts (MEFs). This system provides a generic type of environmentally-mediated protection to the ALL cells, because when the ALL cells are treated with a moderate dose of a therapeutic drug, drug-resistant ALL cells can be recovered after a 1-2 week period of culture. Some of the factors produced by stromal cells that provide protection to ALL cells have been identified. However, it is unclear if the presence of drug-treated ALL cells affects the stromal fibroblasts. The current study was initiated to examine this using expression profiling on the irradiated MEFs.
Publication Title
Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells.
Sample Metadata Fields
Specimen part
View Samples- Escherichia coli str. k-12 substr. mg1655
- 8 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
This study demonstrates simulated microgravity effects on E. coli K 12 MG1655 when grown on LB medium supplemented with glycerol. The results imply that E. coli readily reprograms itself to combat the multiple stresses imposed due to microgravity. Under these conditions it survives by upregulating oxidative stress protecting genes and simultaneously down regulating the membrane transporters and synthases to maintain cell homeostasis.
Publication Title
Effect of simulated microgravity on E. coli K12 MG1655 growth and gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 2000
Description
Genome-wide analyses have identified thousands of long non-coding RNAs (lncRNAs). Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genomic loss, as well as systemic knockdown of Malat1 using antisense oligonucleotides, in the MMTV-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by differentiation into highly cystic tumors and a significant reduction in lung metastasis. Further, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT and Her2/neu amplified tumor organoids consistent with the in vivo reduction in lung metastasis. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and pro-tumorigenic signaling pathways. Together, these data indicate that the lncRNA Malat1 regulates critical processes in mammary cancer pathogenesis and represents a promising therapeutic target for inhibiting breast cancer metastasis. Overall design: Transcriptome profiles of tumors and organoids after Malat1 knockdown using antisense olgonucleotides (ASOs).
Publication Title
Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 20 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We used microarrays to detail the global program of gene expression in response to expression of either mutant (C96Y) or wild-type human proinsulin and identified distinct classes of up-regulated genes. Results provides insight into the molecular mechanisms underlying a form of neonatal diabetes.
Publication Title
Genetic complexity in a Drosophila model of diabetes-associated misfolded human proinsulin.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus, Homo sapiens
- 71 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
Sample Metadata Fields
Specimen part
View Samples