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GSE10902
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The LIM-only protein FHL2 acts as a transcriptional modulator that positively or negatively regulates multiple signaling pathways. We recently reported that FHL2 cooperates with CBP/p300 in the activation of -catenin/TCF target gene cyclin D1. In this paper, we demonstrate that FHL2 is associated with the cyclin D1 promoter at the TCF/CRE site, providing evidence that cyclin D1 is a direct target of FHL2. We show that deficiency of FHL2 greatly reduces the proliferative capacity of spontaneously immortalized mouse fibroblasts which is associated with decreased expression of cyclin D1 and p16INK4a, and hypophosphorylation of Rb. Reexpression of FHL2 in FHL2-null fibroblasts efficiently restores cyclin D1 levels and cell proliferative capacity, indicating that FHL2 is critical for cyclin D1 activation and cell growth. Moreover, ectopic cyclin D1 expression is sufficient to override growth inhibition of immortalized FHL2-null fibroblasts. Gene expression profiling revealed that FHL2 deficiency triggers a broad change of the cell cycle program that is associated with downregulation of several G1/S and G2/M cyclins, E2F transcription factors and DNA replication machinery, thus correlating with reduced cell proliferation. This change also involves downregulation of the negative cell cycle regulators, particularly INK4 inhibitors, which could counteract the decreased expression of cyclins, allowing cells to grow. Our study illustrates that FHL2 can act on different aspects of the cell cycle program to finely regulate cell proliferation.
Publication Title
The LIM-only protein FHL2 regulates cyclin D1 expression and cell proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 34 Downloadable Samples
Illumina HiSeq 2000
Description
An increasing number of non-coding RNAs (ncRNAs) are implicated in various human diseases including cancer; however ncRNA transcriptome of hepatocellular carcinoma (HCC) remains largely unexplored. We use CAGE (Cap Analysis of Gene Expression) to comprehensively map transcription start sites (TSSs) across different etiologies of human HCC as well as mouse HCC, with particular emphasis on ncRNAs distant from protein-coding genes. We find thousands of significantly up-regulated distal ncRNAs in HCC tumors compared to their matched non-tumors, which are as many as protein-coding genes. Moreover, we identify many LTR retroviral promoters activated in HCC tissues and expressed in a subfamily-specific manner, which account for approximately 20% of the up-regulated distal ncRNAs. The transcripts derived from LTRs, determined by 3'' RACE, are multi-exon nuclear ncRNAs typically 0.5-2kb in length. This study sheds light on ncRNA transcriptome of human and mouse HCC. Overall design: Expression profiles using CAGE for 37 mouse HCC. The human data are archived at dbGaP (phs000885.v1.p1). An umbrella BioProject has been created to associate the GEO and dbGaP BioProjects: PRJNA278792
Publication Title
Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Hepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/�-catenin signaling. Microarray analysis identified two tumor subclasses resembling distinct phases of liver development, and a 16-gene signature discriminated invasive and metastatic hepatoblastomas, and predicted prognosis with high accuracy. <br></br>
Publication Title
Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The W-Beijing family of Mycobacterium tuberculosis (Mtb) strains is known for its high-prevalence and -virulence, as well as for its genetic diversity, as recently reported by our laboratories and others. However, little is known about how the immune system responds to these strains. To explore this issue, here we used reverse engineering and genome-wide expression profiling of human macrophage-like THP-1 cells infected by different Mtb strains of the W-Beijing family, as well as by the reference laboratory strain H37Rv. Detailed data mining revealed that host cell transcriptome responses to H37Rv and to different strains of the W-Beijing family are similar and overwhelmingly induced during Mtb infections, collectively typifying a robust gene expression signature ("THP1r2Mtb-induced signature"). Analysis of the putative transcription factor binding sites in promoter regions of genes in this signature identified several key regulators, namely STATs, IRF-1, IRF-7, and Oct-1, commonly involved in interferon-related immune responses. The THP1r2Mtb-induced signature appeared to be highly relevant to the interferon-inducible signature recently reported in active pulmonary tuberculosis patients, as revealed by cross-signature and cross-module comparisons. Further analysis of the publicly available transcriptome data from human patients showed that the signature appears to be relevant to active pulmonary tuberculosis patients and their clinical therapy, and be tuberculosis specific. Thus, our results provide an additional layer of information at the transcriptome level on mechanisms involved in host macrophage response to Mtb, which may also implicate the robustness of the cellular defense system that can effectively fight against genetic heterogeneity in this pathogen.
Publication Title
An interferon-related signature in the transcriptional core response of human macrophages to Mycobacterium tuberculosis infection.
Sample Metadata Fields
Cell line
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- Escherichia coli
- 6 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Mutation of marA, rob, and soxS causes a clinical strain of E.coli to be attenuated at d3 post-infection in a mouse model of pyelonephritis, here we extract RNA at d2 post infection to analyze transcriptional differences between the two strains.
Publication Title
SoxS increases the expression of the zinc uptake system ZnuACB in an Escherichia coli murine pyelonephritis model.
Sample Metadata Fields
Specimen part
View Samples- 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
- 4 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
Analysis of gene expression profiles in MEF cell lines in the absence or presence of STAT3 following IFNa stimulation. This study is to unveil possible role of STAT3 during type I IFN-mediated gene induction and functions.
Publication Title
STAT3 negatively regulates type I IFN-mediated antiviral response.
Sample Metadata Fields
Cell line
View Samples