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GSE8432
Glycine max
26 Downloadable Samples
Affymetrix Soybean Genome Array (soybean)
Description
Affymetrix soybean genome arrays were used to identify genes differentially expressed in the immune resistance response at 6, 12, 24, and 48 hours after inoculation with Phakopsora pachyrhizi isolates TW72-1 or HW94-1
Publication Title
A microarray analysis for differential gene expression in the soybean genome using Bioconductor and R.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
C/EBPb is an auto-repressed protein that becomes posttranslationally activated by Ras-MEK-ERK signalling. C/EBPb is required for oncogene-induced senescence (OIS) of primary fibroblasts, but also displays pro-oncogenic functions in many tumour cells. Here, we show that C/EBPb activation by H-RasV12 is suppressed in immortalized/transformed cells, but not in primary cells, by its 30 untranslated region (30UTR). 30UTR sequences inhibited Ras-induced cytostatic activity of C/EBPb, DNA binding, transactivation, phosphorylation, and homodimerization, without significantly affecting protein expression. The 30UTR suppressed induction of senescence-associated C/EBPb target genes, while promoting expression of genes linked to cancers and TGFb signalling. An AU-rich element (ARE) and its cognate RNA-binding protein, HuR, were required for 30UTR inhibition. These components also excluded the Cebpb mRNA from a perinuclear cytoplasmic region that contains activated ERK1/2, indicating that the site of C/EBPb translation controls de-repression by Ras signalling. Notably, 30UTR inhibition and Cebpb mRNA compartmentalization were absent in primary fibroblasts, allowing Ras-induced C/EBPb activation and OIS to proceed. Our findings reveal a novel mechanism whereby non-coding mRNA sequences selectively regulate C/EBPb activity and suppress its anti-oncogenic functions.
Publication Title
3'UTR elements inhibit Ras-induced C/EBPβ post-translational activation and senescence in tumour cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances and ER stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here we show that C/EBP:ATF4 heterodimers, but not C/EBP:ATF4 dimers, are the predominant CARE binding species in stressed cells. C/EBP and ATF4 associate with genomic CAREs in a mutually-dependent manner and co-regulate many ISR genes. By contrast, the C/EBP family members C/EBP and CHOP were largely dispensable for induction of stress genes. Cebpg/ MEFs proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg/ mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBP-deficient newborns die from atelectasis and respiratory failure which can be mitigated by in utero exposure to the anti-oxidant, N-acetyl-cysteine. Cebpg/ mice on a mixed strain background show improved viability but, upon aging, develop significantly fewer malignant solid tumors compared to WT animals. Our findings identify C/EBP as a novel anti-oxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells.
Publication Title
C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
C/EBP is an important regulator of oncogene-induced senescence (OIS). Here we show that C/EBP, a heterodimeric partner of C/EBP whose biological functions are not well understood, inhibits cellular senescence. Cebpg-/- MEFs proliferated poorly, entered senescence prematurely, and expressed a pro-inflammatory gene signature, including elevated levels of senescence-associated secretory phenotype (SASP) genes whose induction by oncogenic stress requires C/EBP. The senescence-suppressing activity of C/EBP required its ability to heterodimerize with C/EBP. Covalently linked C/EBP homodimers (~) inhibited the proliferation and tumorigenicity of RasV12-transformed NIH3T3 cells, activated SASP gene expression, and recruited the CBP co-activator in a Ras-dependent manner, whereas ~ heterodimers lacked these capabilities and efficiently rescued proliferation of Cebpg-/- MEFs. C/EBP depletion partially restored growth of C/EBP-deficient cells, indicating that the increased levels of C/EBP homodimers in Cebpg-/- MEFs inhibit proliferation. The proliferative functions of C/EBP are not restricted to fibroblasts, as hematopoietic progenitors from Cebpg-/- bone marrow also displayed impaired growth. Furthermore, high CEBPG expression correlated with poorer clinical prognoses in several human cancers, and C/EBP depletion decreased proliferation and induced senescence in lung tumor cells. Our findings demonstrate that C/EBP neutralizes the cytostatic activity of C/EBP through heterodimerization, which prevents senescence and suppresses basal transcription of SASP genes.
Publication Title
C/EBPγ suppresses senescence and inflammatory gene expression by heterodimerizing with C/EBPβ.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st), Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Probe Name version)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placentas role has been a focus. We hypothesized that decidual defects are an important determinant of the placental phenotype. We isolated (human) endometrial stromal cells (hESCs) from non-pregnant donors with a prior pregnancy that was complicated by severe PE (sPE). Versus controls, they failed to decidualize as demonstrated by morphological criteria and the analysis of stage-specific antigens. These results were bolstered by showing that they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal-fetal interface. Transcriptional profiling revealed sPE-associated defects in gene expression. Also, decidual cells from sPE patients, which de-differentiated in vitro, failed to re-decidualize in culture. Immediately following isolation they released factors that inhibited CTB invasion, linking a possible cause to a known effect. These data suggested that failed decidualization is an important contributor to down regulated CTB invasion in sPE. Diagnosis of this defect prior to pregnancy would enable therapies that are designed to improve decidualization, a novel strategy for prevention.
Publication Title
Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gestational protein restriction is a model for low birth size. We hypothesized that taurine supplementation would protect against changes in newborn liver and muscle caused by a maternal low protein diet.
Publication Title
Gestational protein restriction in mice has pronounced effects on gene expression in newborn offspring's liver and skeletal muscle; protective effect of taurine.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Genes encoding transcription factors function as hubs in gene regulatory networks because they encode DNA-binding proteins, which bind to promoters that carry their binding sites. In the present work we have studied gene regulatory networks defined by genes with transcripts belonging to different mRNA abundance classes in the small intestinal epithelial cell. The focus is the rewiring that occurs in transcription factor hubs in these networks during the differentiation of the small intestinal epithelial cell while it migrates along the crypt-villus axis and during its development from a fetal endodermal cell to a mature adult villus epithelial cell.
Publication Title
Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy.
Publication Title
Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.
Sample Metadata Fields
Treatment
View Samples