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GSE6718
Rattus norvegicus
39 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Sustained caloric restriction (CR) extends lifespan in animal models but the mechanism and primary tissue target(s) have not been identified. Gene expression changes with aging and CR were examined in both heart and subcutaneous white adipose tissue (WAT) of F344 male rats using Affymetrix RAE 230 arrays and validated by qRT-PCR on 18 genes. In heart, age- associated changes but not CR-associated changes in old. In WAT, genes were identified where the aging change is suppressed by CR (candidate markers of healthy aging) and those affected by CR but not normal aging (candidate longevity assurance genes). 10-21% of age-associated genes were regulated in common between tissues. Gene set enrichment analysis (GSEA) revealed coordinate small magnitude changes in ribosomal, proteasomal, and mitochondrial genes with similarities between heart and WAT. Further analysis revealed PPARgamma as a potential upstream regulator of altered gene expression in old CR WAT. These results demonstrate a reduced mRNA response to CR with age in heart relative to WAT. In WAT, we identified candidate CR mimetic targets and candidate markers of healthy aging. These data suggest a role for subcutaneous WAT in the effects of CR and strengthen the role for PPAR signaling in aging and CR while indicating that the effects of CR in heart can occur independent of global changes in mRNA level.
Publication Title
Transcriptional response to aging and caloric restriction in heart and adipose tissue.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Expression analysis of genes potentially regulated by BMPRII and beta-catenin. BMPRII has been linked as a genetic factor to the disease pulmonary arterial hypertension.
Publication Title
Disruption of PPARγ/β-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
IlluminaHiSeq2000
Description
Some of the functions and mechanisms of PPAR?-mediated regulation of vascular homeostasis have been revealed, the potential role of PPAR? in angiogenesis is obscure. In human ECs, PPAR?-deficiency was studied using siRNA strategy and RNA sequencing was utilized to reveal angiogenesis-associated targets for PPARg. Overall design: Our aim is to reveal the possible role of PPARy in angiogenesis.
Publication Title
Loss of PPARγ in endothelial cells leads to impaired angiogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 4000
Description
Maintaining endothelial cells (EC) as a monolayer in the vessel wall depends on a gene expression profile and the metabolic state, features influenced by contact with neighboring cells eg, pericytes and smooth muscle cells (SMC). Dysfunctional bone morphogenetic protein receptor 2 (BMPR2) signaling disrupts EC metabolism and monolayer formation and is associated with vascular diseases such as pulmonary arterial hypertension. We show that BMPR2 in either EC or SMC is required for contact-dependent activation of Notch1 in EC. Notch1, through the glycolysis inducer PFKFB3, mediates an increase in the citrate pool and histone acetylation required for Notch1 and MYC target gene expression. This maintains Notch1-dependent EC proliferative capacity, coordinating with Notch1 activation of mitochondria. We report how Notch1 and p300 binding to chromatin and H3K27ac status are influenced by glucose metabolism and regulate gene expression in endothelial cells. Overall design: Examination of RNA-sequencing in pulmonary artery endothelial cells with or without PFKFB3 silencing in contact co-culture with pulmonary artery smooth muscle cells.
Publication Title
Smooth Muscle Contact Drives Endothelial Regeneration by BMPR2-Notch1-Mediated Metabolic and Epigenetic Changes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
The goal of this study is to compare transcriptome profiling (RNA-seq) in controls, unaffected BMPR2 mutation carriers and affected familial pulmonary arterial hypertension patients, to elucidate a protective feature in iPS derived endothelial cells from the mutation carriers. Overall design: mRNA profiles of iPSC-ECs from unrelated control (n=3), unaffected BMPR2 mutation carriers (n=3) and FPAH patients with BMPR2 mutation (n=5).
Publication Title
Patient-Specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect against Pulmonary Hypertension in BMPR2 Mutation Carriers.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
rGal1 (recombinant Galectin-1) vs non treated (Ctrl) pancreatic cancer cell line RWP-1
Publication Title
Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
To understand why cancer vaccine-induced T cells often fail to eradicate tumors, we studied immune responses in mice vaccinated with gp100 peptide emulsified in incomplete Freund's adjuvant (IFA), commonly used in clinical cancer vaccine trials. After gp100 peptide/IFA vaccination, tumor-specific CD8+ T cells (adoptively transferred from gp100-specific TCR-transgenic pmel-1 mice) accumulated not in tumors but at the persisting, antigen-rich vaccination site. Once there, primed T cells became dysfunctional and underwent antigen-driven, IFN- and FasL-mediated apoptosis, resulting in systemic hyporesponsiveness to subsequent vaccination. Provision of anti-CD40 antibody, TLR7 agonist and interleukin-2 (covax) reduced T cell apoptosis but did not prevent vaccination site sequestration. A non-persisting vaccine formulation shifted T cell localization towards tumors, inducing superior anti-tumor activity. Short-lived formulation also reduced systemic T cell dysfunction and promoted memory formation, as shown by gene expression profiling and other measures. Persisting peptide/IFA vaccine depots, currently used to vaccinate cancer patients, can induce specific T cell sequestration at vaccination sites followed by dysfunction and deletion; short-lived depot formulations may overcome these limitations and result in greater therapeutic efficacy of peptide-based cancer vaccines.
Publication Title
Persistent antigen at vaccination sites induces tumor-specific CD8⁺ T cell sequestration, dysfunction and deletion.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina Genome Analyzer II
Description
Here we characterize the changes in the forebrain transcriptome resulting from the deletion of the transcription factor Lhx6, generated by RNA-seq technology with biologic replication. Lhx6 is an essential regulatory gene in the development of cortical interneurons generated in the medial ganglionic eminences of the embryonic brain. This data contains insights into gene networks important for the development of medial ganglionic eminence derived interneurons. Overall design: Forebrain total RNA profiles of 15-day old Lhx6 heterozygote (Het) and Lhx6 null mice were generated by deep sequencing, using Illumina GAIIx. Mutant allele used was Lhx6tm2Vpa (MGI:3702518). Each individual sample was comprised of two animals. Four samples for Lhx6 Het and three samples for Lhx6 null mice were generated and analysed in parallel.
Publication Title
Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex.
Sample Metadata Fields
Cell line, Subject
View Samples- Danio rerio
- 30 Downloadable Samples
- IlluminaHiSeq2000
Description
Regeneration requires cells to regulate proliferation and patterning according to their spatial position. Positional memory is a property that enables regenerating cells to recall spatial information from the uninjured tissue. Positional memory is hypothesized to rely on gradients of molecules, few of which have been identified. Here, we quantified the global abundance of transcripts, proteins and metabolites along the proximodistal axis of caudal fins of uninjured and regenerating adult zebrafish. Using this approach, we uncovered complex overlapping expression patterns for hundreds of molecules involved in diverse cellular functions, including developmental and bioelectric signaling as well as amino acid and lipid metabolism. Moreover, 32 genes differentially expressed at the RNA level had concomitant differential expression of the encoded proteins. Thus, the identification of proximodistal differences in levels of RNAs, proteins, and metabolites will facilitate future functional studies of positional memory during appendage regeneration. Overall design: RNA-seq was performed on 5 biological replicates for each of 3 positions along the proximodistal axis of the caudal fin; proximal, middle and distal (15 total samples). Each biological replicate was a pool of fin regions cut from 2 male and 2 female zebrafish.
Publication Title
Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
mRNA regulation by the circadian protein Nocturnin in A549 cells. Overall design: Total RNA from WT and NOCT KO A549 cells were subject to poly-A pulldown and RNA-seq.
Publication Title
The metabolites NADP<sup>+</sup> and NADPH are the targets of the circadian protein Nocturnin (Curled).
Sample Metadata Fields
Cell line, Subject
View Samples