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GSE11436
Homo sapiens
12 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the DNA damage response, an inducible process required for the suppression of malignancy. The Mre11 complex is predominantly required for repair and checkpoint activation in S phase, while Chk2 governs apoptosis. We examined the relationship between the Mre11 complex and Chk2 in the DNA damage response via the establishment of Nbs1B/B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice. Chk2 deficiency did not modify the checkpoint defects or chromosomal instability of Mre11 complex mutants; however, the double mutant mice exhibited synergistic defects in DNA damage-induced p53 regulation and apoptosis. Nbs1B/B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice were also predisposed to tumors. In contrast, DNA-PKcs deficient mice, in which G1-specific chromosome breaks are present, did not exhibit synergy with Chk2-/- mutants. These data suggest that Chk2 suppresses the oncogenic potential of DNA damage arising during S and G2 phases of the cell cycle.
Publication Title
Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Notch1 signaling is absolutely essential for steady-state thymic lymphopoiesis, but the role of other Notch receptors, and their potential overlap with the function of Notch1, remains unclear. Here we show that like Notch1, Notch3 is differentially expressed by progenitor thymocytes, peaking at the DN3 progenitor stage. Using mice carrying a gene-trapped allele, we show that thymic cellularity is slightly reduced in the absence of Notch3, although progression through the defined sequence of TCR- development is normal, as are NKT and TCR cell production.
Publication Title
Nonoverlapping functions for Notch1 and Notch3 during murine steady-state thymic lymphopoiesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Exercise attenuates the development of chronic non-communicable diseases (NCDs). Gene signaling pathway analysis offers an opportunity to discover if electrically induced muscle exercise regulates key pathways among people living with spinal cord injury (SCI). We examined short-term and long-term durations of electrically induced skeletal muscle exercise on complex gene signaling pathways, specific gene regulation, and epigenetic tagging of PGC1a, a major transcription factor in skeletal muscle of men with SCI. After short or long-term electrically induced exercise training, participants underwent biopsies of the trained and untrained muscles. RNA was hybridized to an exon microarray and analyzed using a gene set enrichment analysis. We discovered that long-term exercise training regulated the Reactome gene sets for Metabolism (38 gene sets), Cell Cycle (36 gene sets), Disease (27 gene sets), Gene Expression and Transcription (22 gene sets), Organelle Biogenesis (4 gene sets), Cellular Response to Stimuli (8 gene sets), Immune System (8 gene sets), Vesicle Mediated Transport (4 gene sets), and Transport of Small Molecules (3 gene sets). Specific gene expression included: Oxidative catabolism of glucose including PDHB (p<0.001), PDHX (p<0.001), MPC1 (p<0.009), and MPC2 (p<0.007); Oxidative phosphorylation genes including SDHA (p<0.006), SDHB (p<0.001), NDUFB1 (p<0.002), NDUFA2 (p<0.001); Transcription Genes including PGC1α (p<0.030) and PRKAB2 (p<0.011); Hypertrophy gene MSTN (p<0.001); and the Myokine generating FNDC5 gene (p<0.008). Long-term electrically induced exercise de-methylated the major transcription factor, PGC1a. Taken together, these findings support that long term electrically induced muscle activity regulates key pathways associated with muscle health and systemic metabolism.
Publication Title
Impact of short- and long-term electrically induced muscle exercise on gene signaling pathways, gene expression, and PGC1a methylation in men with spinal cord injury.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Mus musculus
- 33 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Interaction of hematopoietic progenitors with the thymic stromal microenvironment induces them to proliferate, adopt the T cell fate, and asymmetrically diverge into multiple T lineages. Progenitors at various developmental stages are stratified among different regions of the thymus, implying that the corresponding microenvironments differ from one another, and provide unique sets of signals to progenitors migrating between them. The nature of these differences remains undefined. Here we use novel physical and computational approaches to characterize these stromal subregions, distinguishing gene expression in microdissected tissues from that of their lymphoid constituents. Using this approach, we comprehensively map gene expression in functionally distinct stromal microenvironments, and identify clusters of genes that define each region. Quite unexpectedly, we find that the central cortex lacks distinctive features of its own, and instead appears to function by sequestering unique microenvironments found at the cortical extremities, and modulating the relative proximity of progenitors moving between them.
Publication Title
Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
We used a novel approach to study the acute effect of three physiologic stressors (active contractions, vibration, and systemic heat stress) in human skeletal muscle. Three hours after the completion of a dose of physiologic stress, we sampled the soleus (contraction and vibration) or vastus lateralis (heat) muscle and developed a unique gene expression signature for each stressor. We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold change), PGC-1 (5.46 fold change), and ABRA (5.98 fold change); and repressed MSTN (0.56 fold change). Heat stress repressed PGC-1 (0.74 fold change); while vibration induced FOXK2 (2.36 fold change). Vibration similarly caused a down regulation of MSTN (0.74 fold change), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 while heat stress repressed PGC-1 (0.74 fold change) and ANKRD1 genes (0.51 fold change). These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.
Publication Title
Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
BACKGROUND: The vast majority of thoracic aortic aneurysms (TAAs) are observed either together with a bicuspid aortic valve (BAV), a common congenital disorder, or in idiopathic cases such as patients with a normal tricuspid aortic valve (TAV). The main objective of our study was to identify shared and unique gene expression properties underlying the aortic dilation of BAV and TAV patients.
Publication Title
Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic valve patients with thoracic aortic dilatation: the ASAP study.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Differential expression was used to access gene differences after Entamoeba histolytica infection.
Publication Title
The expression of REG 1A and REG 1B is increased during acute amebic colitis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (E). Here, we report that the E-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD) with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of E-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors.
Publication Title
Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The molecular mechanisms of neurogenic fate determination are of particular importance in light of the need to regenerate neurons. However the molecular logic of neurogenic fate determination is still ill understood, even though some key transcription factors have been implicated. Here we describe how one of these, the transcription factor Pax6, regulates adult neurogenesis by initiating a cross-regulatory network of 3 transcription factors executing neuronal fate and regulating genes required for neuronal differentiation. This network is initiated and driven to sufficiently high expression levels by the transcription factor Pax6 in close interaction with Brg1-containing SWI/SNF chromatin remodeling factors.
Publication Title
The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples