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SRP008123
Mus musculus
12 Downloadable Samples
Illumina Genome Analyzer IIx
Description
The purpose of this study was to determine whether postdevelopmental myostatin depletion influenced the changes in skeletal muscle gene expression profiles induced by a long-term increase in physical activity. Myostatin levels in muscles of adult male mice with floxed myostatin genes were reduced ~85% by activating Cre recombinase. Control mice with normal myostatin genes had the same Cre-activating treatment. Some of the mice were housed in ordinary cages throughout the study, limiting their physical activity. Other mice were given free access to running wheels for the final 12 weeks of the study. At the end of the study, comprehensive gene expression profiles of triceps brachii muscles were determined by RNA sequencing (RNA-Seq), with muscles from mice selected for similarity of running behavior throughout the period of wheel access. Wheel running increased expression of hundreds of mRNAs encoding proteins involved in oxidative energy metabolism, and this response was not affected by myostatin deficiency. The running-induced increase in the ratio of Myh1 mRNA (which encodes myosin heavy chain type 2x) to Myh4 mRNA (which encodes myosin heavy chain type 2b) also was not affected by myostatin depletion. At every threshold of P (computed by analysis of variance), the number of transcripts with interactions between activity level and myostatin level was fewer than the number expected by chance. These data suggest that myostatin is not required for transcriptional adaptations to moderate-intensity exercise. Overall design: 12 samples, 6 from sedentary mice and 6 from active (wheel running) mice. 3 control and 3 myostatin-deficient mice within each activity level.
Publication Title
Synergistic and antagonistic interplay between myostatin gene expression and physical activity levels on gene expression patterns in triceps Brachii muscles of C57/BL6 mice.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 47 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cellular senescence is a program of irreversible cell cycle arrest that normal cells undergo in response to progressive shortening of telomeres, changes in telomeric structure, oncogene activation or oxidative stress. The underlying signalling pathways, potentially of major clinicopathological relevance, are unknown. A major stumbling block to studying senescence has been the absence of suitable model systems because of the asynchrony of this process in heterogeneous cell populations. To simplify this process many investigators study oncogene-induced senescence due to expression of activated oncogenes where senescence occurs prematurely without telomere attrition and can be induced acutely in a variety of cell types. We have taken a different approach by making use of the finding that reconstitution of telomerase activity by introduction of the catalytic subunit of human telomerase alone is incapable of immortalising all human somatic cells, but inactivation of the p16-pRB and p53-p21 pathways are required in addition. The ability of SV40 large T antigen to inactivate the p16-pRB and p53-p21 pathways has enabled us to use a thermolabile mutant of LT antigen, in conjunction with hTERT, to develop conditionally immortalised human (HMF3A) fibroblasts that are immortal but undergo an irreversible growth arrest when the thermolabile LT antigen is inactivated leading to activation of pRB and p53. When these cells cease dividing, senescence-associated- b-galactosidase activity is induced and the growth-arrested cells have morphological features and express genes in common with senescent cells. Since these cells growth arrest in a synchronous manner they are an excellent starting point for dissecting the pathways that underlie cellular senescence and act downstream of p16-pRB and p53-p21 pathways. We have combined genome-wide expression profiling with genetic complementation to undertake identification of genes that are differentially expressed when these conditionally immortalised human fibroblasts undergo senescence upon activation of the p16-pRB and p53-p21 tumour suppressor pathways.
Publication Title
Activation of nuclear factor-kappa B signalling promotes cellular senescence.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 81 Downloadable Samples
- Illumina HiSeq 2500
Description
Agonistic encounters with conspecifics are powerful effectors of future behavior that evoke strong and durable neurobiological responses. We recently identified a deeply conserved “toolkit” of transcription factors (TFs) that respond to social challenge across diverse species in coordination with distinct conserved signatures of energy metabolism and developmental signaling. To further characterize this response and its transcriptional drivers in mice, we examined gene expression and chromatin landscape in the hypothalamus, frontal cortex, and amygdala of socially challenged and control animals over time. The data revealed a complex spatiotemporal pattern of metabolic, neural, and developmental transcriptomic signatures coordinated with significant shifts in the accessibility of distally located regulatory elements. Transcriptional regulatory network and motif analyses revealed an interacting network of TFs correlated with differential gene expression across the tissues and time points we assayed, including the early-acting and conserved regulator of energy metabolism and development, ESRRA. Cell-type deconvolution analysis attributed the early metabolic activity implicated by our transcriptomic analysis primarily to oligodendrocytes and the developmental signal to neurons, and we confirmed the presence of ESRRA in both oligodendrocytes and neurons throughout the brain. To assess the role of this nuclear receptor as an early trigger of this coordinated response, we used chromatin immunoprecipitation to map ESRRA binding sites to a set of genes involved in metabolic regulation and enriched in challenge-associated differentially expressed genes. Together, these data support a rich model linking metabolic and neural responses to social challenge, and identify regulatory drivers with unprecedented tissue and temporal resolution. Overall design: Territory-holding resident mice were males from the C57BL/6J strain co-housed with females to establish a territory. Intruder mice were males from the BALB/C strain. Animals were housed in a 12L:12D animal room until the resident-intruder paradigm was undertaken. Before behavior work, male C57BL/6J animals were cohoused with members of the same sex for two weeks, housed alone for a week, and then housed with a single C57BL/6J female for a week to establish a territory. Thus, before behavior work, the animals were allowed to habituate to our animal facility for four weeks. Three hours before testing, females were removed from the resident males’ cages. Immediately before the trial, residents’ cages were inserted into a blank-walled chamber. For experimental mice, we introduced unfamiliar intruder BALB/cJ male mice. Intruders were contained within a stainless steel wire ~1cm mesh cage to prevent animals from making contact and injuring one another. Control animals were exposed to the same cage, but containing a paper cup instead of an intruder mouse. The cages were removed in both intruder and control conditions after five minutes. After exposure to the intruder or control stimulus, resident animals were allowed to sit in a dark and quiet place for either 30 minutes, 60 minutes, or 120 minutes. Residents were then immediately euthanized by cervical dislocation. As soon as animals were euthanized, we extracted three brain regions of interest from our animals: frontal cortex, hypothalamus, and amygdala. This yielded tissue samples from which RNA was extracted. The RNA samples were pooled to generate libraries for sequencing. For control mice there were 5 replicates for all combinations of time after stimulus (30, 60, 120 minutes) and brain region (frontal cortex, hypothalamus, amygdala) except for hypothalamus from control mice after 30 minutes (3 replicates) and for frontal cortex from control mice after 120 minutes (6 replicates). For experimental mice there were 5 replicates for all combinations of time after stimulus (30, 60, 120 minutes) and brain region (frontal cortex, hypothalamus, amygdala) except for frontal cortex from experimental mice after 120 minutes (6 replicates).
Publication Title
Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
An efficient innate immune recognition of the intracellular parasite T. cruzi is crucial for host protection against development of Chagas disease, which often leads to multiple organ damage, particularly the heart leading to cardiomyopathy. Mechanisms modulated by MyD88 have been shown to be necessary for resistance against T, cruzi infection. Recently, Nod-like receptors have been shown to play an important role as innate immune sensors, particularly as they relate to inflammasome function, caspase activation, and inflammatory cytokine production. In this study, we aimed to investigate the participation of innate immune responses in general, and inflammasomes in particular, in heart inflammation and cardiac damage upon infection with the T. cruzi parasite.
Publication Title
Apoptosis-associated speck-like protein containing a caspase recruitment domain inflammasomes mediate IL-1β response and host resistance to Trypanosoma cruzi infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in the liver
Publication Title
Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in epididymal adipiose tissue (EWAT)
Publication Title
Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Macrophage polarization between the M2 (repair, pro-tumorigenic) and M1 (inflammatory) phenotypes is seen as a continuum of states. The detailed transcriptional events and signals downstream of CSF-1R that contribute to amplification of the M2 phenotype and suppression of the M1 phenotype are largely unknown. Macrophage CSF-1R pTyr-721 signaling promotes cell motility and enhancement of tumor cell invasion in vitro. Combining analysis of cellular systems for CSF-1R gain-of-function and loss-of-function with bioinformatic analysis of the macrophage CSF-1R pTyr-721-regulated transcriptome, we uncovered miR-21 as a downstream molecular switch controlling macrophage activation and identified ERK1/2 and NF-B as CSF-1R pTyr-721-regulated signaling nodes. We show that CSF-1R pTyr-721 signaling suppresses the proinflammatory phenotype, predominantly by induction of miR-21. Profiling of the miR-21-regulated mRNAs revealed that 80% of the CSF-1-regulated canonical miR-21 targets are pro-inflammatory molecules. Additionally, miR-21 positively regulates M2 marker expression. Moreover, miR-21 feeds back to positively regulate its own expression and to limit CSF-1R-mediated activation of ERK1/2 and NF-B. Consistent with an anti-inflammatory role of miRNA-21, intraperitoneal injection of mice with a miRNA-21 inhibitor increases the recruitment of inflammatory monocytes and enhances the peritoneal monocyte/macrophage response to lipopolysaccharide (LPS).
Publication Title
Colony stimulating factor-1 receptor signaling networks inhibit mouse macrophage inflammatory responses by induction of microRNA-21.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Renal recovery following injury relies on cellular regeneration. In the mouse kidney following injury, injured epithelial cells undergoes de-differentiate, proliferate and re-differentiate into functional cells, following a a tightly controlled genetic programme where specific sets of genes are up-regulated.
Publication Title
Histone deacetylase inhibitor enhances recovery after AKI.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human B cell lineage acute lymphoblastic leukemia (ALL) cells carrying MLL-AF4 (SEM; BEL) and E2A-PBX1 (697) gene rearrangements were transduced with the mouse ecotropic receptor to permit subsequent entry of retroviral BCR-ABL1 GFP and GFP empty vectors (EV) pseudotyped with murine ecotropic envelope. GFP expression was measured by flow cytometry. Transductions with BCR-ABL1 GFP and GFP empty vectors (EV) were performed in the presence and absence of 2 mmol/l Imatinib (TKI). Washout of Imatinib in one series of experiments is indicated with an arrow. To study gene expression changes in MLL-AF4 and E2A-PBX1 B cell lineage ALL cells that were transduced with empty vectors (EV), BCR-ABL1 GFP in the presence of Imatinib (BCR-ABL1 OFF), washout of Imatinib (BCR-ABL1 ON) and subsequent re-addition of Imatinib, microarray analyses were performed.
Publication Title
Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner.
Sample Metadata Fields
Specimen part
View Samples