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SRP026364
Mus musculus
14 Downloadable Samples
Illumina Genome Analyzer IIx
Description
We have generated “reprogrammable” transgenic mice that ubiquitously express the four Yamanaka factors in an inducible manner. Transitory induction of the transgene results in multiple teratomas emerging from a variety of organs, thus indicating that full reprogramming into iPSCs can occur in vivo. By performing bone marrow transplant experiments, we demonstrate that both hematopoietic cells, as well as non-hematopoietic cells can be reprogrammed in vivo. Remarkably, reprogrammable mice also present circulating iPSCs in the bloodstream (in vivo-iPSCs) with all the expected properties of bona fide iPSCs. Moreover, in contrast to in vitro-iPSCs or embryonic stem cells (ESCs), in vivo-iPSCs have an increased capacity to undergo trophectoderm lineage differentiation, which suggests that in vivo-iPSCs are more plastic or primitive than in vitro-generated iPSCs or ESCs. Overall design: 6 clones of in vivo-generated iPSCs, 5 indendent clones of in vitro-generated iPSCs, and 3 clones of established ESCs
Publication Title
Reprogramming in vivo produces teratomas and iPS cells with totipotency features.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Multipotent pancreatic progenitors (MPC) are defined as Ptf1a+, Mychigh, Cpa+ cells. During the transition from MPC to unipotent acinar progenitors, c-Myc is down-regulated whereas Ptf1a is up-regulated, leading to the deployment of the acinar program. Here, we show that c-Myc and Ptf1a interact directly and c-Myc binds to, and represses, the transcriptional activity of the PTF1 complex in vitro and in vivo. Using Ela1-Myc mice, in which c-Myc is overexpressed in acinar cells starting at E14.5, we find that acinar cells fail to undergo normal maturation at P1 and this is followed by a massive subsequent repression of the acinar programme. Lineage tracing with Ptf1aCreERT2;Rosa26YFP and Ela1-Myc;Ptf1aCreERT2;Rosa26YFP mice receiving TMX at E15.5 and analyzed at E18.5 revealed that c-Myc overexpression is associated with activation of a hepatic programme but not with pancreatic lineage misspecification At 8 weeks, the silencing of the acinar program is associated with increased expression of the PRC2 complex in a c-Myc dependent manner. Genome wide studies show that Ptf1a and c-Myc display partially overlapping chromatin occupancy patterns and DNA binding competition. We conclude that c-Myc down-regulation during development is crucial for the maturation of pre-acinar to acinar cells. c-Myc overexpression may contribute to pancreatic carcinogenesis by restraining cell differentiation and rendering cells susceptible to transformation. Overall design: Pancreas mRNA profiles of 8-week old wild type (WT) and ELA1-MYC mice were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Publication Title
c-Myc downregulation is required for preacinar to acinar maturation and pancreatic homeostasis.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Gene expression changes in 3 human melanoma cell lines were compared to freshly isolated normal primary melanocytes Overall design: Three biological replicates for each melanoma cell line and primary melanocytes were labeled and run Illumina HiSeq2500. The transcriptome of melanocytes was compared to cell line SK-Mel-28, SK-Mel-147 or UACC-62.
Publication Title
Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Purpose: Asess the transcritpional changes induced upon RAB7 knock-down in melanoma (SK-Mel-28 and UACC-62) and in colon cancer (HCT-116) cell lines. Methods: mRNA profiles of tumor cell lines (SK-Mel-28, UACC-62, HCT-116) stably expressing scrambled shRNA or RAB7 shRNA (harvested at day 3 after lentiviral infection) were generated by deep sequencing, using three biological replicates per condition. The sequence reads that passed quality filters were analyzed with TopHat and Cufflinks. Validation of induced / silenced genes was performed by western blot. Results show a differential impact of RAB7 expression in the transcriptomic profile of melanoma vs non-melanoma cell lines, and support a lineage-specific role of this small GTPase in melanoma. Overall design: Examination of the mRNA profiles RAB7-depleted vs wild type cells, performed in parallel in 3 different tumor cell lines (Melanomas: SK-Mel-28 and UACC-62, Non-melanoma: HCT-116) harvested at day 3 after lentiviral infection.
Publication Title
RAB7 controls melanoma progression by exploiting a lineage-specific wiring of the endolysosomal pathway.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Tissue-specific differentiation and inflammatory programmes are thought to independently contribute to disease. The orphan nuclear receptor NR5A2 is a key regulator of pancreas differentiation, and SNPs in and near the human gene are associated with risk of pancreatic cancer. In mice, Nr5a2 heterozygosity sensitizes the pancreas to damage, impairs regeneration, and cooperates with mutant Kras in tumor progression. Through transcriptomic analysis, we uncovered a basal pre-inflammatory state in the pancreas of heterozygous mice that is reminiscent of pancreatitis-induced inflammation and is conserved in histologically normal human pancreata with reduced Nr5a2 mRNA expression. In mice, Nr5a2 undergoes a dramatic transcriptional switch from tissue-specific to inflammatory loci, which promotes AP-1-dependent inflammatory gene transcription. Deletion of c-Jun in the pancreas of Nr5a2+/- mice rescues the pre-inflammatory phenotype and the defective regenerative response to damage. These findings provide compelling evidence that the same transcriptional networks supporting homeostasis in normal tissue can be subverted to foster inflammation upon genetic or environmental constraints. Overall design: A mild acute pancreatitis was induced by seven hourly injections of the CCK analog caerulein (Bachem) at 50 ug/kg. Briefly, animals were weighted before the beginning of the procedure and caerulein was administered i.p. Mice were sacrificed by cervical dislocation 8h, 24h,and 48h after the first injection. Three animals of each genotype and timepoint were analysed.
Publication Title
Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
Gene expression analysis in hLECs treated with gain of function or loss of function of MDK in human melanoma cells. Overall design: Biological triplicates of hLEC treated for 3 days with EGM-2 MV conditioned media of melanoma cells. Cell line SK-Mel-147 KD for MDK (shMDK) and its corresponding control (shCtrl (LoF) and WM164 cell line overexpressing MDK (MDK) or an empty vector (NEG) (GoF) were used to produce the conditioned media.
Publication Title
Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 84 Downloadable Samples
- IlluminaHiSeq2000
Description
Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders. Overall design: Total RNA obtained from skin explants taken from psoriatic patients or healthy donors cultured in the presence of AhR agonist or antagonist
Publication Title
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders.
Publication Title
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Differential gene expression was analyzed for FACS sorted Math1::Cre; ROSA-tdTomato from hand dissected cochlear nuclei of wild type and Hoxa2/Hoxb2 mutant mice Overall design: In order to investigate the role of Hoxa2 and Hoxb2 transcription factors in a subset of cells of the cochlear nucleus, we generated double conditional knock-out by crossing the deleter line Math1::Cre crossed with Rosa tdTomato; Hoxa2fl/fl; Hoxb2fl/fl and Rosa tdTomato wild type background. FACS sorted cells from hand dissected cochlear nuclei were than processed and RNA-seq performed (see extract protocol and library construction protocol).
Publication Title
Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem.
Sample Metadata Fields
No sample metadata fields
View Samples