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GSE7050
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Activation of b-catenin has been causatively linked to the etiology of colon cancer. Conditional stabilization of this molecule in pro-T-cells promotes thymocyte development without the requirement for preTCR signaling. We show here that activated b-catenin stalls the developmental transition from the double-positive (DP) to the single-positive (SP) thymocyte stage and predisposes DP thymocytes to transformation. b-Catenin induced thymic lymphomas have a leukemic arrest at the early DP stage. Lymphomagenesis requires Rag activity, which peaks at this developmental stage, as well as additional secondary genetic events. A consistent secondary event is the transcriptional upregulation of c-Myc, whose activity is required for transformation since its conditional ablation abrogates lymphomagenesis. In contrast, the expression of Notch receptors as well as targets is reduced in DP thymocytes with stabilized b-catenin and remains low in the lymphomas indicating that Notch activation is not required or selected for in b-catenin induced lymphomas. Thus, b-catenin activation may provide a mechanism for the induction of T-ALL that does not depend on Notch activation.
Publication Title
Beta-catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Although transcriptional programs associated with T-cell specification and commitment have been described, the functional hierarchy and the roles of key regulators in structuring/ orchestrating these programs remain unclear. Activation of Notch signaling in uncommitted precursors by the thymic stroma initiates the T-cell differentiation program. One regulator first induced in these precursors is the DNA binding protein Tcf-1, a T-cell specific mediator of Wnt signaling. Yet the specific contribution of Tcf-1 to early T-cell development and the signals inducing it in these cells remain unclear. Here we assign functional significance to Tcf-1 as a gatekeeper of T-cell fate. We show that Tcf-1 is directly activated by Notch signals. Tcf-1 is required at the earliest phase of Tcell determination for progression beyond the early thymic progenitor (ETP) stage. The global expression profile of Tcf-1 deficient progenitors indicates that basic processes of DNA metabolism are downregulated in its absence and the blocked T-cell progenitors become abortive and die by apoptosis. Our data thus add an important functional relationship to the roadmap of T-cell development.
Publication Title
T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2u Nucleosome Remodeling and Deacetylase (NuRD) complex is controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethers this complex to active lymphoid differentiation genes, but keeps it in a functionally-poised state. Loss in Ikaros DNA binding activity causes a local increase in Mi-2u chromatin remodeling, histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributes to transcriptionally-poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their re-activation. Thus release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally-opposing epigenetic mechanisms and genetic networks.
Publication Title
Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Caenorhabditis elegans
- 47 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Transgenic animals were engineered to express human amyloid peptide controlled by a muscle-specific, heat-inducible promoter. At low temperatures (16C) Abeta expression is minimal, while at higher temperatures (20-25C) Abeta accummulates in large quantities and causes paralysis.
Publication Title
Identifying Aβ-specific pathogenic mechanisms using a nematode model of Alzheimer's disease.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 54 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Melanoma-associated Antigen gene family (MAGE) generally encodes for tumour antigens. We recently have identified one of the MAGE gene members, Mageb16 to be highly expressed in undifferentiated murine embryonic stem cells (mESCs). The role of Mageb16 for the differentiation of the pluripotent stem cells is completely unknown. Here we demonstrate that Mageb16 (41 kDa) is distributed in cytosol and/or in surface membrane in undifferentiated mESCs. A transcriptome study was performed with differentiated short hairpin RNA (shRNA)-mediated Mageb16 knockdown (KD ESCs) and scrambled control (SCR) ESCs until a period of 22 days. Mageb16 KD ESCs mainly differentiated towards mesodermal derivatives such as cardiovascular lineages. Mesoderm-oriented differentiation initiated biological processes such as adipogenesis, osteogenesis, limb morphogenesis and spermatogenesis were significantly enriched in the differentiated Mageb16 KD ESCs. Cardiomyogenesis in differentiated KD mESCs was stronger when compared to differentiated SCR and wild mESCs. The expression of non-coding RNA (ncRNA) Lin28a and other epigenetic regulatory genes, nucleocytoplasmic trafficking and genes participating in spermatogenesis have also declined faster in the differentiating Mageb16 KD ESCs. We conclude that Mageb16 plays a crucial role for differentiation of ESCs, specifically to the mesodermal lineages. Regulative epigenetic networks and nucleocytoplasmic modifications induced by Mageb16 may play a role for the critical role of Mageb16 for the ESCs differentiation.
Publication Title
Depletion of Mageb16 induces differentiation of pluripotent stem cells predominantly into mesodermal derivatives.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 32 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
ICU acquired weakness (ICUAW) is a complication of critical illness characterized by structural and functional impairment of skeletal muscle that may persist for years after ICU discharge with many survivors developing protracted courses with few regaining functional independence. Elucidating molecular mechanisms underscoring sustained ICUAW is crucial to understanding outcomes linked to different morbidity trajectories as well as for the development of novel therapies. Quadriceps muscle biopsies and functional measures of muscle strength and mass were obtained at 7 days and 6 months post-ICU discharge from a cohort of ICUAW patients. Unsupervised co-expression network analysis of transcriptomic profiles identified discrete modules of co-expressed genes associated with the degree of muscle weakness and atrophy in early and sustained ICUAW. Modules were enriched for genes involved in skeletal muscle regeneration and extracellular matrix deposition. Collagen deposition in persistent ICUAW was confirmed by histochemical stain. Modules were further validated in an independent cohort of critically ill patients with sepsis-induced multi-organ failure and a porcine model of ICUAW, demonstrating disease-associated conservation across species and peripheral muscle type. Our findings provide a pathomolecular basis for sustained ICUAW, implicating aberrant expression of distinct skeletal muscle structural and regenerative genes in early and persistent ICUAW.
Publication Title
Transcriptomic analysis reveals abnormal muscle repair and remodeling in survivors of critical illness with sustained weakness.
Sample Metadata Fields
Sex, Age
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Comparative analysis of Endodermal-like cell lines with demonstrated ability to support myocardial differentiation
Publication Title
A comparative analysis of extra-embryonic endoderm cell lines.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Metazoan transcription is controlled through either coordinated recruitment of transcription machinery to the gene promoter, or subsequently, through regulated pausing of RNA polymerase II (Pol II) in early elongation. We report that a key difference between genes that use these distinct regulatory strategies lies in the chromatin architecture specified by their DNA sequences. Pol II pausing is prominent at highly-regulated genes whose sequences inherently disfavor nucleosome formation within the gene, but favor nucleosomal occlusion of the promoter. Pausing of polymerase maintains these genes in an active state by inhibiting the formation of repressive promoter chromatin. In contrast, promoters of housekeeping genes that lack paused Pol II are deprived of nucleosomes regardless of polymerase binding, but show higher nucleosome occupancy downstream. Our results suggest that the default chromatin state of a gene instructs its regulation, and that highly-regulated promoters have evolved to encourage competition between nucleosomes and paused Pol II for promoter occupancy.
Publication Title
Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Dengue is one of the most important arboviruses in the world, with 2.5 billion people living in areas under risk to contagious. Mosquitos from Aedes genus is the transmission vector of viral particles.
Publication Title
Single point mutations in the helicase domain of the NS3 protein enhance dengue virus replicative capacity in human monocyte-derived dendritic cells and circumvent the type I interferon response.
Sample Metadata Fields
Specimen part, Time
View Samples