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SRP185924
Caenorhabditis elegans
14 Downloadable Samples
Illumina HiSeq 2500
Description
Purpose: We observed protein homeostasis modulations when anc-1 is knocked-down. We wanted to measure changes in gene expression profiles following this manipulation. Methods: We treated wild type (strain N2) or polyQ35-YFP (strain AM140) nematodes, which express toxic aggregative proteins that challenge their protein homeostasis, with anc-1 RNAi until day six of adulthood, and compared their gene expression levels to those of untreated worms. Results: The knockdown of anc-1 leads to modified expression levels of hundreds of genes. There is an enrichment of transcription factors and protein homeostasis modulators, such as E3 ubiquitin ligases. Conclusions: anc-1 regulates protection from toxic aggregative proteins, at least partially, by regulating the expression of genes that encode protein homeostasis factors. Overall design: Wild type strain, three repeats; polyQ35-YFP strain, four repeats. Each repeat has two conditions: untreated (EV), and RNAi toward anc-1.
Publication Title
Gene expression modulation by the linker of nucleoskeleton and cytoskeleton complex contributes to proteostasis.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The objective of this study is to identify the genes that are up-regulated amid proteasome dysfunction to facilitate the discovery of proteolytic pathways that are activated as a compensatory response to proteasome inhibition. Proteasome is a large multi-component proteolytic complex in the cell. It is responsible for the constitutive turn-over of many cellular proteins as well as the degradation of oxidized and/or unfolded proteins. With such a fundamental role in the cell, disruption of proteasome understandably can lead to disastrous outcome. Oxidative stress has been postulated as the driving mechanism for aging. Oxidatively modified proteins, which usually have lost their activity, require immediate removal by proteasome to maintain normal cellular function. Dysfunction of proteasome has also been linked to neuro-degenerative diseases such as Alzheimers and Parkinsons diseases, those that are most commonly seen in aged population. There is more than one proteolytic pathway in the cell, and it has been reported that obstruction of any one of these pathways may enhance the activity of the others. Proteasomal function has been found to have decreased during aging, prompting researchers to hypothesize that failure to remove oxidized proteins may play an important role in aging. It would be interesting to determine the other proteolytic pathways that are activated after proteasome inhibition by a relatively specific inhibitor epoxomicin to help understand their roles in aging processes.
Publication Title
Iron regulatory protein 2 turnover through a nonproteasomal pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant. This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele specific mutant p53 dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. These data identify NSC319726 as a p53R175 mutant reactivator and as a lead compound for p53 targeted drug development.
Publication Title
Allele-specific p53 mutant reactivation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- NextSeq 500
Description
The mammalian brain is complex, with multiple cell types performing a variety of diverse functions, but exactly how each cell type is affected in aging remains largely unknown. Here we performed a single-cell transcriptomic analysis of young and old mouse brains. We provide comprehensive datasets of aging-related genes, pathways and ligand–receptor interactions in nearly all brain cell types. Our analysis identified gene signatures that vary in a coordinated manner across cell types and gene sets that are regulated in a cell-type specific manner, even at times in opposite directions. These data reveal that aging, rather than inducing a universal program, drives a distinct transcriptional course in each cell population, and they highlight key molecular processes, including ribosome biogenesis, underlying brain aging. Overall, these large-scale datasets provide a resource for the neuroscience community that will facilitate additional discoveries directed towards understanding and modifying the aging process. Overall design: Total of 16 mice brains with raw data for 50,212 single cells and processed data for 37,089 single cells
Publication Title
Single-cell transcriptomic profiling of the aging mouse brain.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Foxp3+ regulatory T cells (Treg cells) maintain immunological tolerance and their deficiency results in fatal multi-organ autoimmunity. Although heightened T cell receptor (TCR) signaling is critical for the differentiation of Treg cells, the role of TCR signaling in Treg cell function remains largely unknown. Here we demonstrate inducible ablation of the TCR results in Treg cell dysfunction which cannot be attributed to impaired Foxp3 expression, decreased expression of Treg cell signature genes or altered ability to sense and consume interleukin 2. Rather, TCR signaling was required for maintaining the expression of a limited subset of genes comprising 25% of the activated Treg cell transcriptional signature. Our results reveal a critical role for the TCR in Treg cell suppressor capacity.
Publication Title
Continuous requirement for the TCR in regulatory T cell function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation, an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic stem cells (ESCs). Loss of H3K27me3 leads to a failure of ESCs to properly differentiate, which presents a major roadblock for dissecting the precise roles of PRC2 activity during lineage commitment. While recent studies suggest that loss of H3K27me3 leads to changes in DNA methylation in ESCs, how these two pathways coordinate to regulate gene expression programs during lineage commitment is poorly understood. Here, we analyzed gene expression and DNA methylation levels in several PRC2 mutant ESC lines that maintain varying levels of H3K27me3. We found that maintenance of intermediate levels of H3K27me3 allowed for proper temporal activation of lineage genes during directed differentiation of ESCs to spinal motor neurons (SMNs). However, genes that function to specify other lineages failed to be repressed, suggesting that PRC2 activity is necessary for lineage fidelity. We also found that H3K27me3 is antagonistic to DNA methylation in cis. Furthermore, loss of H3K27me3 leads to a gain in promoter DNA methylation in developmental genes in ESCs and in lineage genes during differentiation. Thus, our data suggest a role for PRC2 in coordinating dynamic gene repression while protecting against inappropriate promoter DNA methylation during differentiation. Overall design: Embryonic Stem Cell (ESC) lines mutant for PRC2 core components Suz12 (Suz12GT and Suz12delta) and Eed (Eednull) were subjected to in vitro directed differentiation down the spinal motor neuron lineage. ESCs and day 5 differentiated cells from the three mutant lines and wild-type were used for RNA-seq.
Publication Title
Polycomb Repressive Complex 2 regulates lineage fidelity during embryonic stem cell differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 17 Downloadable Samples
- NextSeq 500
Description
RNA-seq of Wild Type (N2), pmk-1 or atf-7 mutant animals exposed to either non-pathogenic E. coli OP50 or pathogenic P. aeruginosa PA14 Overall design: mRNA profiles were generated using 3 replicates (>1,000 animals each) of each condition were prepared and sequenced, except for atf-7(qd22qd130) on PA14 which had only 2 replicates. Sequenced on Illumina NextSeq 500
Publication Title
Global transcriptional regulation of innate immunity by ATF-7 in C. elegans.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
Adult stem cells support tissue homeostasis and repair throughout the life of an individual. However, numerous intrinsic and extrinsic changes occur with age that result in altered stem cell behavior and reduced tissue maintenance and regeneration. In the Drosophila testis, stem cells surround and contact the apical hub, a cluster of somatic cells that express the self-renewal factor Unpaired (Upd), which activates the JAK-STAT pathway in adjacent stem cells. However, aging results in a dramatic decrease in upd expression, with a concomitant loss of germline stem cells (GSCs). Here we present genetic and biochemical data to demonstrate that IGF-II mRNA binding protein (Imp) counteracts endogenous small interfering RNAs to stabilize upd RNA and contribute to maintenance of the niche. However, Imp expression decreases in hub cells of older males, similar to upd, which is due to targeting of Imp by the heterochronic microRNA let-7. Therefore, in the absence of Imp, upd mRNA becomes unprotected and susceptible to degradation. Understanding the mechanistic basis for aging-related changes in stem cell behavior will lead to the development of strategies to treat age-onset diseases and facilitate stem cell based therapies in older individuals. Overall design: Examination of small RNA levels in testes from young (1day old) and aged (30days old) males of Drosophila melanogaster by deep sequencing (using Illumina GAII).
Publication Title
The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Anopheles gambiae
- 62 Downloadable Samples
- Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Developmental and evolutionary basis for drought tolerance of the Anopheles gambiae embryo.
Sample Metadata Fields
No sample metadata fields
View Samples- Anopheles gambiae
- 56 Downloadable Samples
- Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
In order to examine the gene expression in the course of mosquito embryogenesis, microarray assays were performed on staged A. gambiae embryos, from fertilization to 52 hours of development (which is close to hatching at ~50 hours post-fertilization). RNA was extracted from staged embryos roughly every three hours after fertilization, and then hybridized to the A. gambiae transcriptome microarray.
Publication Title
Developmental and evolutionary basis for drought tolerance of the Anopheles gambiae embryo.
Sample Metadata Fields
No sample metadata fields
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