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GSE28711
Mus musculus
23 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Polycomb function during oogenesis is required for mouse embryonic development.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In mammals, totipotent pre-implantation embryos are formed by fusion of highly differentiated oocytes and spermatozoa. Acquisition of totipotency concurs with remodeling of chromatin states of parental genomes (epigenetic reprogramming), changes in maternally contributed transcriptome and proteome, and zygotic genome activation. Genomes of mature germ cells are more proficient in supporting embryonic development than those of somatic cells. It is currently unknown whether transgenerational inheritance of chromatin states present in mature gametes underlies the efficacy of early embryonic development after natural conception. Here, we show that Ring1 and Rnf2, two core components of the Polycomb Repressive Complex 1 (PRC1), serve redundant gene regulatory functions during oogenesis that are required to support embryonic development beyond the two-cell stage. Numerous developmental regulatory genes that are established Polycomb targets in various somatic cell types are de-repressed in Ring1/Rnf2 double mutant (dm) fully grown germinal vesicle (GV) oocytes. Translation of tested aberrant maternal transcripts is, however, delayed until after fertilization. Exchange of maternal pro-nuclei between control and Ring1/Rnf2 maternally dm early zygotes demonstrates an essential role for Ring1 and Rnf2 during oogenesis in defining cytoplasmic and nuclear maternal contributions that are both essential for proper initiation of embryonic development. A large number of genes up-regulated in Ring1/Rnf2 dm GV oocytes harbor PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) in spermatozoa and in embryonic stem cells (ESCs), and are repressed during normal oogenesis and early embryogenesis. These data strongly support the model that Polycomb acts in the female and male germline to silence differentiation inducing genes and to program chromatin states, thereby sustaining developmental potential across generations.
Publication Title
Polycomb function during oogenesis is required for mouse embryonic development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In mammals, totipotent pre-implantation embryos are formed by fusion of highly differentiated oocytes and spermatozoa. Acquisition of totipotency concurs with remodeling of chromatin states of parental genomes (epigenetic reprogramming), changes in maternally contributed transcriptome and proteome, and zygotic genome activation. Genomes of mature germ cells are more proficient in supporting embryonic development than those of somatic cells. It is currently unknown whether transgenerational inheritance of chromatin states present in mature gametes underlies the efficacy of early embryonic development after natural conception. Here, we show that Ring1 and Rnf2, two core components of the Polycomb Repressive Complex 1 (PRC1), serve redundant gene regulatory functions during oogenesis that are required to support embryonic development beyond the two-cell stage. Numerous developmental regulatory genes that are established Polycomb targets in various somatic cell types are de-repressed in Ring1/Rnf2 double mutant (dm) fully grown germinal vesicle (GV) oocytes. Translation of tested aberrant maternal transcripts is, however, delayed until after fertilization. Exchange of maternal pro-nuclei between control and Ring1/Rnf2 maternally dm early zygotes demonstrates an essential role for Ring1 and Rnf2 during oogenesis in defining cytoplasmic and nuclear maternal contributions that are both essential for proper initiation of embryonic development. A large number of genes up-regulated in Ring1/Rnf2 dm GV oocytes harbor PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) in spermatozoa and in embryonic stem cells (ESCs), and are repressed during normal oogenesis and early embryogenesis. These data strongly support the model that Polycomb acts in the female and male germline to silence differentiation inducing genes and to program chromatin states, thereby sustaining developmental potential across generations.
Publication Title
Polycomb function during oogenesis is required for mouse embryonic development.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 191 Downloadable Samples
Illumina HiSeq 3000
Description
High endothelial venules (HEVs) are specialized blood vessels allowing recirculation of naïve lymphocytes through lymphoid organs. Here, using full length single-cell RNA sequencing, RNA-FISH, flow cytometry and immunohistofluorescence, we reveal the heterogeneity of HEVs in adult mouse peripheral lymph nodes (PLNs) under conditions of homeostasis, antigenic stimulation and after inhibition of lymphotoxin-b receptor (LTbR) signaling. We demonstrate that HEV endothelial cells are in an activated state during homeostasis, and we identify the genes characteristic of the differentiated HEV phenotype. We show that LTbR signaling regulates many HEV genes and pathways in resting PLNs, and that immune stimulation induces a global and temporary inflammatory phenotype in HEVs without compromising their ability to recruit naïve lymphocytes. Most importantly, we uncover differences in the regulation of genes controlling lymphocyte trafficking, Glycam1, Fut7, Gcnt1, Chst4, B3gnt3 and Ccl21a, that have implications for HEV function and regulation in health and disease. Overall design: Comparison of High Endothelial Cells and Blood Endothelial Cells from mouse lymph nodes under 4 different conditions with a total of 220 single cells.
Publication Title
Single-Cell Analysis Reveals Heterogeneity of High Endothelial Venules and Different Regulation of Genes Controlling Lymphocyte Entry to Lymph Nodes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcriptome study of 2 Saccharomyces cerevisiae W303 derivatives, one carrying GFP (control) and one carrying aSyn-GFP
Publication Title
Different 8-hydroxyquinolines protect models of TDP-43 protein, α-synuclein, and polyglutamine proteotoxicity through distinct mechanisms.
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Humoral responses of mice specifically deleted for Moz (a histone acetyltransferase) or c-Myb (a transcription factor) in B cells were aberrant. RNA-sequencing analysis was performed to assess gene expression differences compared to wild-type controls in germinal center B cells or plasmablasts. Overall design: Moz f/f Aicda1-Cre, Aicda1-Cre, Myb f/f Cd23-Cre, Mybf/f (no cre) mice were immunized with NP-KLH precipitated in alum and germinal center B cells were sort-purified. Secondary plasmablasts were sort-purified from immunized mice boosted with NP-KLH in PBS (Myb experiment). Two independent experiments were conducted.
Publication Title
Regulation of germinal center responses and B-cell memory by the chromatin modifier MOZ.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Acetylation and deacetylation of histones and other proteins depend on the opposing activities of histone acetyltransferases and histone deacetylases (HDACs), leading to either positive or negative gene expression changes. The use of HDAC inhibitors (HDACi) has uncovered a role for HDACs in the control of proliferation, apoptosis and inflammation. However, little is known of the roles of specific HDACs in intestinal epithelial cells (IEC). We investigated the consequences of ablating both Hdac1 and Hdac2 in murine IECs gene expression.
Publication Title
HDAC1 and HDAC2 restrain the intestinal inflammatory response by regulating intestinal epithelial cell differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500
Description
BRAF oncogene is mutated in ~50% of human cutaneous melanomas. The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway fuelling cancer growth. The inhibitors of BRAF V600E (BRAFi), lead to massive and high response rate. However, BRAFi-resistant cells that operate as a cellular reservoir for relapses severely limits the duration of the clinical response. The recent depiction of these resistant cells did not identify druggable targets to ensure long-term survival under BRAFi. Here, we identify the aryl hydrocarbon receptor (AhR) as a target to eradicate resistant cells. We show that BRAFi bind to AhR on a new site, named beta-pocket, and reprogram gene expression independently of its partner ARNT. beta-pocket activation induces a pigmentation signature, which is associated to BRAFi-induced cell death of sensitive BRAF V600E melanoma cells and tumour shrinkage. Intriguingly, in resistant cells, BRAFi does not induced a pigmentation signature since these cells display another AhR program; AhR-ARNT dependant. By this way, AhR directs several key BRAFi-resistant genes. At single cell level, this constitutive activation of AhR-ARNT is identified in rare cells before BRAFi-treatment of melanoma tumours and an enrichment of these alpha-cells is observed under BRAFi. Our data strongly suggest that an endogenous AhR ligand activates AhR-ARNT via the canonical AhR pocket (alpha-pocket), thus favouring BRAFi-resistant gene expression. Importantly, we identify the clinically compatible AhR antagonist, the resveratrol (RSV), able to abrogate the deleterious constitutive activation of AhR and to reduce the cellular reservoir for the relapse. Taken together, this work reveals that constitutive AhR signalling drives BRAFi resistance and constitutes a therapeutic target to achieve long-term patient survival under BRAFi. More broadly, the constitutive activation of AhR by endogenous ligands is in line with the ability of UV radiations to generate potent AhR ligands and to favour melanoma onset. Overall design: Total RNA isolated from 12 human melanoma cell lines (501Mel) after different treatments was subjected to multiplexed RNA-sequencing using Illumina NextSeq500 sequencing tehnology.
Publication Title
Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The statins are a family of inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase enzyme, which converts acetyl-CoA into mevalonic acid. Since HMG-CoA reductase catalyzes the rate-limiting step in the mevalonate pathway of cholesterol biosynthesis, it was thought that the major clinical benefit of statins was to reduce cholesterol levels in the bloodstream; statins are thus in wide clinical use for the prevention and treatment of cardiovascular disease. Nonetheless, mevalonate is also the precursor of isoprenoid compounds, which are substrates for the post-translational modification of many proteins involved in cell signaling. The blockade of isoprenoid synthesis might explain the pleiotropic effects described for statins in extrahepatic tissues, including inhibition of pathogen infection and anti-inflammatory and immunomodulatory activities.
Publication Title
A lovastatin-elicited genetic program inhibits M2 macrophage polarization and enhances T cell infiltration into spontaneous mouse mammary tumors.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
C.pn potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of Ldlr/ mice. We discovered that C.pn-induced extracellular IL-1 triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. Gpr109a and Abca1 were both upregulated in plaque lesions in Nlrp3/ mice in both hyperlipidemic and C.pn infection models.
Publication Title
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples