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GSE38277
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stem cells reside in specific niches providing stemness-maintaining environments. Thus, the regulated migration from these niches is associated with differentiation onset. However, mechanisms retaining stem cells in their niche remain poorly understood. Here, we show that the epigenetic regulator lysine-specific demethylase 1 (Lsd1) organises the trophoblast niche of the early mouse embryo by coordinating migration and invasion of trophoblast stem cells (TSCs). Lsd1 deficiency leads to the depletion of the stem cell pool resulting from precocious migration of TSCs.
Publication Title
Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
The aim of the study is to identify AR target gens in LNCaP cells Overall design: 6 samples correponding to 2 times 3 replicates were used for the study
Publication Title
Assembly of methylated KDM1A and CHD1 drives androgen receptor-dependent transcription and translocation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
HTETOP cells, derived from the human fibrosarcoma cell line HT1080, express human topoisomearse II (TOP2A) exclusively from a tetracycline (TET)-regulated transgene, we used HTETOP cells to differentiate between TOP2A-dependent and independent apoptotic effects of doxorubicin and dexrazoxane.
Publication Title
Topoisomerase II{alpha}-dependent and -independent apoptotic effects of dexrazoxane and doxorubicin.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 418 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
The carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. Since the results of these 2-year bioassays are not known until quite late during development of new chemical entities, and since the short-term test battery to test for genotoxicity, a characteristic of genotoxic carcinogens, is hampered by low specificity, the identification of early biomarkers for carcinogenicity would be a big step forward. Using gene expression profiles from the livers of rats treated up to 14 days with genotoxic and non-genotoxic carcinogens we previously identified characteristic gene expression profiles for these two groups of carcinogens. We have now added expression profiles from further hepatocarcinogens and from non-carcinogens the latter serving as control profiles. We used these profiles to extract biomarkers discriminating genotoxic from non-genotoxic carcinogens and to calculate classifiers based on the support vector machine (SVM) algorithm. These classifiers then predicted a set of independent validation compound profiles with up to 88% accuracy, depending on the marker gene set. We would like to present this study as proof of the concept that a classification of carcinogens based on short-term studies may be feasible.
Publication Title
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 63 Downloadable Samples
Affymetrix Rat Expression 230A Array (rae230a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 63 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
In this study we performed microarray-based molecular profiling of liver samples from Wistar rats exposed to genotoxic carcinogens (GC), nongenotoxic carcinogens (NGC) or non-hepatocarcinogens (NC) for up to 14 days. In contrast to previous toxicogenomics studies aimed at the inference of molecular signatures for assessing the potential and mode of compound carcinogenicity, we considered multi-level omics data. Besides evaluating the predictive power of signatures observed on individual biological levels, such as mRNA, miRNA and protein expression, we also introduced novel feature representations which capture putative molecular interactions or pathway alterations by integrating expression profiles across platforms interrogating different biological levels.
Publication Title
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Therapeutic efficacy of first-generation hypomethylating agents (HMAs) is limited in elderly acute myeloid leukemia (AML) patients. Therefore, combination strategies with targeted therapies are urgently needed. Here, we discover that priming with SGI-110 (guadecitabine), a next-generation HMA, sensitizes AML cells to ASTX660, a novel antagonist of cellular Inhibitor of Apoptosis Protein 1 and 2 (cIAP1/2) and X-linked IAP (XIAP). Importantly, SGI-110 and ASTX660 synergistically induced cell death in a panel of AML cell lines as well as in primary AML samples while largely sparing normal CD34+ human progenitor cells, underlining the translational relevance of this combination. Unbiased transcriptome analysis revealed that SGI-110 alone or in combination with ASTX660 upregulated the expression of key regulators of both extrinsic and intrinsic apoptosis signaling pathways such as TNFRSF10B (DR5), FAS and BAX. Individual knockdown of the death receptors TNFR1, DR5 and FAS significantly reduced SGI-110/ASTX660-mediated cell death, whereas blocking antibodies for TRAIL or FASLG failed to provide protection. Also, TNF-blocking antibody Enbrel had little protective effect on SGI110/ASTX660-induced cell death. Further, SGI-110 and ASTX660 acted in concert to promote cleavage of caspase-8 and BID, thereby providing a link between extrinsic and intrinsic apoptotic pathways. Consistently, sequential treatment with SGI-110 and ASTX660 triggered loss of mitochondrial membrane potential (MMP) and BAX activation, which contributes to cell death as BAX silencing significantly protected from SGI-110/ASTX660-mediated apoptosis. Together, these events culminated in activation of caspases-3/-7, nuclear fragmentation and cell death. In conclusion, SGI-110 and ASTX660 cooperatively induced apoptosis in AML cells by engaging extrinsic and intrinsic apoptosis pathways, highlighting the therapeutic potential of this combination for AML.
Publication Title
Next-generation hypomethylating agent SGI-110 primes acute myeloid leukemia cells to IAP antagonist by activating extrinsic and intrinsic apoptosis pathways.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Enteric glial cells (EGCs) are the main constituent of the enteric nervous system and share similarities with astrocytes from the central nervous system including their reactivity to an inflammator microenvironment. In this study we isolated GFAP-positive myenteric glia from FVB/hGFAP-eGFP transgenic postnatal day 7 mice. Following cell sorting for the eGFP reporter, GFAP-positive EGCs were cultured for 3 weeks to generate neurosphere-like bodies. This cell culture was stimulated with LPS for 48 h and cells were employed for gene expression profiling. LPS-stimulated cell cultures were compared to untreated control cell cultures. Enriched GFAP+ EGC cultures secreted increased levels of prominent inflammatory cytokines upon LPS stimulation. Further, in vitro cultures were compared to GFAP-eGFP-positive cells directly analyzed after cell sorting of small intestinal LMMP digests (in vivo) to assess alterations in transcriptomic profiles due to the in vitro culture.
Publication Title
Activation of Myenteric Glia during Acute Inflammation In Vitro and In Vivo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
HEK 293 cells were transiently transfected with plasmids expressing Vector only(PCMV), Aire, or MBD-VP16 with the goal of comparing the global gene expression profiles in the Aire and MBD-VP16 groups
Publication Title
The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.
Sample Metadata Fields
Specimen part, Cell line
View Samples