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GSE56843
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
SRC-1 affects the expression of complex I of the mitochondrial electron transport chain, a set of enzymes responsible for the conversion of NADH to NAD(+). NAD(+) and NADH were subsequently identified as metabolites that underlie SRC-1's response to glucose deprivation. Knockdown of SRC-1 in glycolytic cancer cells abrogated their ability to grow in the absence of glucose consistent with SRC-1's role in promoting cellular adaptation to reduced glucose availability
Publication Title
Steroid receptor coactivator 1 is an integrator of glucose and NAD+/NADH homeostasis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Each cell type responds uniquely to stress and fractionally contributes to global and tissue-specific stress responses. Hepatocytes, liver macrophages (M), and sinusoidal endothelial cells (SEC) play functionally important and interdependent roles in adaptive processes such as wound healing, obesity, and tumor growth. Although these cell types demonstrate significant phenotypic and functional heterogeneity, their distinctions enabling disease-specific responses remain understudied. To address this, we developed a strategy for simultaneous isolation and quantification of these liver cell types based on antigenic cell surface marker expression in response to DEN and found that while there was only a marginal increase in hepatocyte number, M and SEC populations were quantitatively increased. Global gene expression profiling of hepatocytes, M and SEC identified characteristic gene fingerprints that define each cell type and their distinct physiological or oncogenic stress signatures. Integration of these cell-specific gene fingerprints with available hepatocellular carcinoma (HCC) patient microarray data demonstrates that the hepatocyte-specific response strongly correlates with the human HCC gene expression profile. Liver-specific M and SEC gene signatures demonstrate significant alterations in inflammatory and angiogenic gene regulatory pathways, which may impact the hepatocyte response to oncogenic stress. Further validation confirms alterations in components of two key pathways, AP-1 and p53, that have been previously associated with HCC onset and progression. Our data reveal unique gene expression patterns that serve as molecular fingerprints for the cell-centric responses to pathologic stimuli in the distinct microenvironment of the liver. The technical advance highlighted in this study provides an essential resource for assessing hepatic cell-specific contributions to oncogenic stress, information that could unveil previously unappreciated molecular mechanisms for the cellular crosstalk that underlies the development of hepatic cancer.
Publication Title
Deciphering hepatocellular responses to metabolic and oncogenic stress.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 4000
Description
To gain insights into the molecular pathogenesis of DCM caused by LMNA mutation, a doxycycline-inducible (Dox-Off) gene expression system was used to express either a wild type (WT) or a mutant LMNA containing the pathogenic variant p.Asp300Asn (LMNAD300N) in cardiac myocytes. The LMNAD300N is associated with DCM in patients with atypical progeroid/Werner syndrome and non-syndromic cardiac progeria. Expression of the mutant LMNAD300N protein in cardiac myocytes led to severe fibrosis, apoptosis, cardiac dysfunction, and premature death. RNA-seq was performed (prior to onset of cardiac dysfunction) to identify gene signatures and transcriptional regulators responsible for this phenotype. Mechanistic studies identified activation of E2F/TP53/DDR, as a major mechanism responsible for the pathogenesis of DCM caused by the LMNAD300N mutation. Overall design: RNA-seq analysis from 2-week old WT and mice expressing mutant LMNA (LMNAD300N)
Publication Title
DNA Damage Response/TP53 Pathway Is Activated and Contributes to the Pathogenesis of Dilated Cardiomyopathy Associated With LMNA (Lamin A/C) Mutations.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 4000
Description
Mutations in the LMNA gene causes set of disorders collectively referred to as laminopathies that include dilated cardiomyopathy. Lamin A/C proteins a components of nuclear lamina forms distinct nuclear domains called lamina associated domains (LADs). The roles of LADs in DCM is not known. To identify LADs and characterize their associations with CpG methylation and gene expression in human cardiac myocytes isolated from patients with DCM and controls we performed Chromatin immunoprecipitation-sequencing (ChIP-Seq), reduced representative bisulfite sequencing (RRBS), and RNA-sequencing (RNA-Seq) in 5 control and 5 DCM hearts with defined pathogenic variants in the LMNA gene. LADs are redistributed in DCM, are associated with CpG methylation and suppressed transcription, contributing to the pathogenesis of DCM in laminopathies. Overall design: integrated analysis of ChIP-seq for LMNA from Cardiac myocytes and RNA-seq and RRBS from 5 control and 5 DCM human heart sample
Publication Title
Genomic Reorganization of Lamin-Associated Domains in Cardiac Myocytes Is Associated With Differential Gene Expression and DNA Methylation in Human Dilated Cardiomyopathy.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Proliferation of prostate cancer cells, LNCaP, is suppressed by casodex. This suppression requires expression of AR coregulator, NCOR1.
Publication Title
Nuclear Receptor Corepressor 1 Expression and Output Declines with Prostate Cancer Progression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
AR transcriptional activity is regulated by DHT
Publication Title
Nuclear Receptor Corepressor 1 Expression and Output Declines with Prostate Cancer Progression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Nuclear receptor (NR)-mediated transcription is a dynamic process that is regulated by the binding of distinct ligands that induce conformational changes in the NR. These molecular alterations lead to the recruitment of unique cofactors (coactivators or corepressors) that control the expression of NR-regulated genes. Here, we show that a stretch of proline residues located within the N-terminus of AR is necessary for maximal androgen-mediated prostate cancer cell growth and migration. Furthermore, this polyproline domain is necessary for the expression of a subset of AR-target genes, but is dispensable for classical AR-mediated gene transcription. Using T7 phage display, we subsequently identified a novel AR-interacting protein, SH3YL1, whose interaction with AR is dependent upon this polyproline domain. Like the AR polyproline domain, SH3YL1 was required for maximal androgen-mediated cell growth and migration. Microarray analysis revealed that SH3YL1 also regulated a subset of AR-modulated genes. Correspondingly, we identified ubinuclein1 (UBN1), a key member of a histone H3.3 chaperone complex, as a transcriptional target of AR/SH3YL1. Moreover, UBN1 was necessary for maximal androgen-mediated proliferation and migration. Collectively, our data link a specific surface located within ARs N-terminus to the recruitment of a novel cofactor, SH3YL1, which is required for the androgen-mediated expression of UBN1. Importantly, this signaling network was important for both androgen-mediated prostate cancer cell growth and migration. This work is significant because it could aid in the development of selective androgen receptor modulators (SARMs) and have therapeutic implications for AR-driven diseases.
Publication Title
Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To determine the global transcriptome changes in mantle cell lymphoma cells following treatment with the BET bromodomain antagonist, JQ1
Publication Title
Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Estrogen signaling pathway is critical for breast cancer development and has remained the major adjuvant therapeutic target for this disease. Tamoxifen has been used in clinic for many years to treat ER-positive breast cancer. However a great many (30%) suffer relapse due to drug resistance. In this study, the bromodomain inhibitor JQ1 was found to down-regulate ERalpha gene expression and have anti-tumor effect in cultured tamoxifen-resisant breast cancer cells.
Publication Title
An epigenomic approach to therapy for tamoxifen-resistant breast cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed an RNA-Seq analysis comparing thymic lymphoma tissues from the p53-null(n=2) and ?Np63?/?;p53-/- (n=3) or ?Np73?/?;p53-/-(n=3). Mice at 10 weeks of age were injected with either Ad-mCherry or Ad-CRE-mCherry to delete ?Np63/?Np73 in the thymic lmyphomas. We aimed to test by deleting the DNp63/DNp73 in these p53-deficient tumors will mediate tumor regression and analyze the expression profile of the genes Overall design: Examination of thymic lymphoma tissues in 3 different genotypes (p53-/- vs ?Np63?/?;p53-/- or ?Np73?/?;p53-/-)
Publication Title
IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples