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GSE5579
Homo sapiens
3 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Lymphatic endothelial cells were grown under normoxia, hypoxia (1% 0xygen) and conditioned medio from NSLCN growth under normoxia or hypoxia. Gene expression was measured and comparition between samples performed
Publication Title
Hypoxia alters the adhesive properties of lymphatic endothelial cells. A transcriptional and functional study.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We have characterized a mutation affecting the Arabidopsis EARLY IN SHORT DAYS 7 (ESD7) gene encoding the catalytic subunit of the DNA polymerase epsilon (e), AtPOL2A. esd7-1 mutations causes early flowering independently of photoperiod, shortened inflorescence internodes and altered leaf and root development. esd7-1 was a hypomorphic allele whereas KO alleles displayed an embryo-lethal phenotype. The SAM and the RAM in the esd7-1 seedlings were found to exhibit an altered disposition that might correlate with the abnormal expression pattern of SAM and RAM marker genes. esd7-1 showed higher sensitivity to DNA damaging reagents than wild type plants and altered expression of genes involved in DNA repair mechanisms by homologous recombination. Moreover, esd7 early flowering phenotype requires functional FT and SOC1 proteins and might be also related to the mis-regulation of AG and AG-like gene expression found in esd7. Loci involved in the modulation of the chromatin structural dynamics, such as TFL2 and EBS, which negatively regulate FT expression, were found to interact genetically with ESD7, and the carboxy terminus of ESD7 interacted with TFL2 in vitro. Besides, fasciata2 (fas2) mutations suppressed esd7 early flowering phenotype and INCURVATA 2 (ICU2) was found to be epistatic to ESD7. Discrete regions of the chromatin of FT and AG loci were enriched in activating epigenetic marks in the esd7-1 mutant. We concluded that ESD7 might be participating in processes involved in chromatin-mediated cellular memory.
Publication Title
EARLY IN SHORT DAYS 7 (ESD7) encodes the catalytic subunit of DNA polymerase epsilon and is required for flowering repression through a mechanism involving epigenetic gene silencing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
We report the RNAseq data obtained from 50.000-100.000 CD31-/CD45- pneumocytes isolated by FACS from mice harboring a normal dose or one extra copy of the Sirt1 gene, and a tamoxifen-inducible oncogenic KI alelle of KRasG12V after 4 weeks of tamoxifen treatment. Pneumocytes with the activated form of the inducible KRasG12V oncogene sere selected making use of the reporter gene LacZ (located next to the oncogene in the same polycistronic mRNA), by loading CD31-/CD45- pneumocytes with the LacZ-activated fuorogenic molecule FDG prior to FACS sorting. Overall design: Four replicates of each genetic group (Sirt1-WT and Sirt1-Tg) pneumocytes were used for this study. Sirt1-WT were used as reference controls.
Publication Title
Sirt1 protects from K-Ras-driven lung carcinogenesis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the RNAseq data obtained from 50.000-100.000 CD31-/CD45- pneumocytes isolated by FACS from mice harboring a normal dose or one extra copy of the Sirt1 gene, and a tamoxifen-inducible oncogenic KI alelle of KRasG12V after 4 weeks of tamoxifen treatment plus 2 weeks without tamoxifen. Pneumocytes with the activated form of the inducible KRasG12V oncogene sere selected making use of the fluorescent reporter gene Katushka (located at an independent locus), by detecting Katushka fluorescence. Overall design: Four replicates of each genetic group (Sirt1-WT and Sirt1-Tg) pneumocytes were used for this study. Sirt1-WT were used as reference controls.
Publication Title
Sirt1 protects from K-Ras-driven lung carcinogenesis.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Estrogens are potential regulators of the hematopoietic stem cell (HSC) niche and have effects on mature hematopoietic cells; however, whether estrogen signaling directly regulates normal and malignant HSC remains unclear. We demonstrate differential expression and specific roles of estrogen receptors (ER) in hematopoietic progenitors. ERa activation in short-term HSC and multipotent progenitors induced apoptosis. In contrast, the selective ER modulator (SERM) tamoxifen induced proliferation of quiescent long-term HSC, altered their self-renewal signature and compromised hematopoietic reconstitution following myelotoxic stress. Treatment with tamoxifen alone abolished hematopoietic progenitor expansion induced by JAK2V617F by restoring normal levels of apoptosis, blocked JAK2V617F-induced myeloproliferative neoplasm in vivo, and sensitized MLL-AF9+ leukemias to chemotherapy. Tamoxifen showed selective effects on mutant cells compared to normal ones, and had only a minor impact on steady-state hematopoiesis in disease-free animals. These results uncover specific regulation of hematopoietic progenitors by estrogens and potential anti-leukemic properties of SERM Overall design: LT-HSCs, ST-HSCs and MPPs sorted from the bone marrow of mice treated with tamoxifen or vehicle (3 biological replicates per group)
Publication Title
Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bladder cancer (BC) is a highly prevalent human disease in which Rb pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here we show that the in vivo inactivation of all Rb family genes in the mouse urothelium is sufficient to initiate BC development. The characterization of the mouse tumors revealed multiple molecular features of human BC, including the activation of E2F transcription factor and subsequent Ezh2 expression, and the activation of several signaling pathways previously identified as highly relevant in urothelial tumors. Whole transcriptional characterizations of the mouse bladder tumors revealed a significant overlap with human BC samples, and a predominant role for Ezh2 in the downregulation of gene expression programs. Importantly, we determined that in human superficial BC patients, the increased tumor recurrence and progression in these recurrences is associated with increased E2F and Ezh2 expression and Ezh2-mediated gene expression repression. Collectively, our studies provide a genetically defined model for human high-grade superficial BC and demonstrate the existence of an Rb-E2F-Ezh2 axis in bladder whose disruption can promote tumor development.
Publication Title
In vivo disruption of an Rb-E2F-Ezh2 signaling loop causes bladder cancer.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Mesenchymal stem cells (MSCs) And osteolineage cells contribute to the hematopoietic stem cell (HSC) Niche in the bone marrow of long bones. However, Their developmental relationships remain unclear. Here we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin- MSCs participate in fetal skeletogenesis, And lose MSC activity soon after birth. In contrast, Quiescent neural-crest-derived nestin+ Cells in the same bones preserve MSC activity, But do not generate fetal chondrocytes. Instead, They differentiate into HSC-niche-forming MSCs, Helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP+ PDGFR- Cell population also contains Schwann-cell precursors, But does not comprise mature Schwann cells. Thus, In the developing bone marrow HSC-niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, And ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation. Overall design: Total RNA was isolated from small numbers of FACS sorted stromal cells, obtained from neonatal Nes-Gfp bone marrow preparations (2 biological replicates). Each independent set of samples was obtained from pooled skeletal elements (long bones and sterna) form multiple littermates.
Publication Title
The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The specific deletion of Rb gene in epidermis leads to altered proliferation and differentiation, but not to the development of spontaneous tumors. Our previous data have demonstrated the existence of a functional compensation of Rb loss by Rbl1 (p107) in as the phenotypic differences with respect to controls are intensified. However, the possible evolution of this aggravated phenotype, in particular in relationship with tumorigenesis, has not been evaluated due to the premature death of the double deficient mice. We have now investigated whether p107 can also act as a tumor suppressor in pRb-deficient epidermis using different experimental approaches. We found spontaneous tumor development in doubly-deficient skin grafts. Moreover, Rb-deficient keratinocytes are susceptible to Ha-ras-induced transformation, and this susceptibility is enhanced by p107 loss. Further functional analyses, including microarray gene expression profiling, indicated that the loss of p107, in the absence of pRb, produces the reduction of p53-dependent pro-apoptotic signals. Overall, our data demonstrate that p107 behaves as a tumor suppressor in epidermis in the absence of pRb and suggest novel tumor-suppressive roles for p107 in the context of functional p53 and activated Ras
Publication Title
p107 acts as a tumor suppressor in pRb-deficient epidermis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Aim: To determine the role of NOTCH during the response-to-injury and subsequent chronic inflammatory process of the arterial wall underlying atherosclerosis. Methods and results: We have generated an endothelial-specific RBPJK depleted mice using the Cdh5 cadherin promoter (ApoE-/-;RBPJflox/flox;Cdh5- CreERT). Endothelial-specific deletion of the Notch effector RBPJK or systemic deletion of the Notch1 receptor in athero-susceptible ApoE-/- mice fed a HC diet for 6 weeks resulted in reduced atherosclerosis in the aortic arch and sinus. Intravital microscopy revealed decreased leukocyte rolling on the endothelium of ApoE-/-;RBPJflox/flox;Cdh5- CreERT, that correlated with the lesser presence of leukocyts and macrophages in the vascular wall. Consistent with this, transcriptome analysis revealed that proinflammatory and endothelial activation pathways were downregulated in atherosclerotic tissue of RBPJk-mutant mice.. Jagged1 signaling upregulation in endothelial cells promotes the physical interaction and nuclear translocation of the intracellular domain of the Notch1 receptor (N1ICD) with NF-kB,. This N1ICD and NF-kB interaction is required for reciprocal transactivation of target genes including vascular cell adhesion molecule-1 (Vcam1). Conclusions: Notch signaling pathway inactivation decreases leukocyte rolling, thereby preventing endothelial dysfunction and vascular inflammation. Thus attenuating Notch signaling may constitute a useful therapeutic strategy for atherosclerosis. Key words: atherosclerosis, endothelium, signaling pathways, Notch, NF-kB, transcriptional regulation Overall design: RNA was isolated from the aortic arches of three ApoE-/-;RBPJflox/flox and three ApoE-/-; RBPJflox/flox;Cdh5-CreERTmice
Publication Title
Endothelial Jag1-RBPJ signalling promotes inflammatory leucocyte recruitment and atherosclerosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression profile between Parp-2-/- and wild-type hematopoietic stem/progenitor cells at basal and to the early response (2.5 hours) to 5 Gy total body irradiation
Publication Title
Parp-2 is required to maintain hematopoiesis following sublethal γ-irradiation in mice.
Sample Metadata Fields
Specimen part
View Samples