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Mus musculus
20 Downloadable Samples
Illumina HiSeq 2000, Illumina Genome Analyzer IIx, Illumina Genome Analyzer II
Description
Purpose: Long non-coding RNAs (lncRNAs) display development-specific gene expression patterns, yet we know little about their precise roles in lineage commitment. Here, we discover a novel mammalian heart-associated lncRNA, AK143260, necessary for cardiac lineage specification. Methods: Gene expression profiles of mouse ESCs and differentiated organs were analyzed for master regulators of lineage commitment. The AK143260 transcript was shown to be strongly expressed in mESCs and in cells undergoing cardiac differentiation. Its role in cardiac differentiation was examined using depletion and in vitro differentiation systems, with morphological and gene expression profiling at different time-points. Results: mESCs depleted of AK143260, named Braveheart, fail to differentiate into cardiomyocytes and to activate a core cardiac gene regulatory network including key transcription factors driving cardiogenesis. We show that Braveheart functions upstream of MesP1 (mesoderm posterior 1), a transcription factor critical for specification of the earliest known multi-potent cardiovascular progenitor and in promoting epithelial-mesenchymal transition (EMT). Consistent with this, Braveheart depletion leads to morphological defects and loss of cardiogenic potential in a defined in vitro cardiomyocyte differentiation system. Furthermore, Braveheart is necessary to maintain myocardial gene expression and myofibril organization in neonatal cardiomyocytes. Conclusions: These findings reveal that Braveheart is an important regulator of cardiac commitment and implicate lncRNAs as potential therapeutic targets for cardiac disease and regeneration. Overall design: Gene expression profiles from control and Bravheart-depleted mESCs were obtained by RNA-Seq on an Illumina HiSeq2000 instruments at Days 0,3,6 and 9. Gene expression profiles from mESCs, MEFs, partially reprogrammed MEFs and miPS cells were obtained by RNA-Seq on Illumina GAII/GAIIx instruments.
Publication Title
Braveheart, a long noncoding RNA required for cardiovascular lineage commitment.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Transcriptome of murine testis from wild type mice and mice lacking telomerase for three generations (G3-Terc), Ku86 or both telomerase and Ku86.
Publication Title
Effectors of mammalian telomere dysfunction: a comparative transcriptome analysis using mouse models.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE2684- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Recent studies suggest that telomerase promotes cell growth by mechanisms that extend beyond the rescue of critically short telomeres. The in vitro model of mTert overexpressing MEFs recapitulates fundamental aspects of the growth-promoting effects of mTert in vivo. First, in Terc-proficient cells, mTert overexpression favors escape from replicative senescence and enhances anchorage-independent growth in response to oncogenic stress, which fits well with previous data showing that mTert overexpression promotes tumor formation. Second, in Terc-deficient cells, retroviral transduction with mTert results in a delayed onset of immortalization and impairs colony formation in response to oncogenic stress, which is in agreement with the inhibitory effect of mTert overexpression on tumorigenesis in a Terc null mouse background. To unravel the molecular targets of telomerase that impact on cell growth, we compared the transcriptome of MEFs, before and after mTert introduction. We found that ectopic expression of mTert was associated with detectable gene expression changes (greater than 1.5-fold; validated by qRT-PCR) of 26 transcripts. Analysis of the observed transcriptional changes indicates that ectopic expression of mTert suppresses in a coordinated manner functionally related genes with overlapping roles in growth arrest, resistance to transformation, and apoptosis. We show that the majority of the telomerase target genes are growth-inhibitory, transforming growth factor-beta (TGF-beta) -inducible genes and provide functional evidence for the potential of telomerase to abrogate TGF-beta -mediated growth inhibition. Thus, in line with the current view that the diversity of TGF-beta responses is not so much a consequence of the use of different signaling pathways but caused by different ways of reading the output from the same basic pathway, we propose that the telomerase status of a cell creates a gene expression pattern that determines how cells read growth inhibitory signals, among them signals propagated through the TGF-beta pathway.
Publication Title
Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta
- 59 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
CD8+ T-cells inhibit virus replication in SIV-infected rhesus macaques (RM). However, it is unclear to what extent the viral suppression mediated by CD8+ T-cells reflects direct killing of infected cells as opposed to indirect, non-cytolytic mechanisms. In this study, we used functional genomics to investigate potential mechanisms of in vivo viral suppression mediated by CD8+ lymphocytes. Eight chronically SIVmac239-infected RMs underwent CD8+ lymphocyte depletion, and RNA from whole blood was obtained prior to depletion, at the nadir of CD8+ lymphocytes (5 days post-depletion), and during the repopulation phase (11 days post-depletion). Principal components analysis demonstrated that overall gene expression during the nadir of CD8+ T-cells was highly divergent from other intervals. Conversely, the genomic signature of samples from the CD8+ cell rebound phase was similar to that of pre-depletion samples. During CD8+ lymphocyte depletion we detected a strongly significant decrease in the expression of the genes encoding CD8 and CD8 chains, consistent with the near complete CD8+ T-cell depletion measured by flow cytometry. Of note, we observed significant down-regulation of the expression of genes encoding for factors that can suppress SIV replication, including the CCR5-binding chemokine CCL5/Rantes, several retroviral restriction factors (TRIM10, TRIM15, APOBEC3G/H) and defensins. Reduced expression of various genes related to T cell activation and proliferation was also observed. Collectively, these data indicate that depletion of CD8+ lymphocytes in SIV-infected RMs is associated with the establishment of a pattern of gene expression that may result in increased intrinsic permissivity to virus replication.
Publication Title
Transcriptional profiling of experimental CD8(+) lymphocyte depletion in rhesus macaques infected with simian immunodeficiency virus SIVmac239.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Clinicians need additional metrics for predicting quality of human oocytes for IVF procedures. Human polar bodies reflect the oocyte transcript profile. Quantitation of polar body mRNAs could allow for both oocyte ranking and embryo preferences in IVF applications. The transcriptome of a polar body has never been reported, in any organism. Overall design: Eight total samples. There are 2 biological replicates of the following four conditions: pooled oocytes and their sister polar bodies and a single oocyte and its sister polar body.
Publication Title
The transcriptome of a human polar body accurately reflects its sibling oocyte.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The transcription factor BATF is required for Th17 and TFH differentiation. Here, we show that BATF also has a fundamental role in regulating effector CD8+ T cell differentiation. BATF-deficient CD8+ T cells show profound defects in effector expansion and undergo proliferative and metabolic catastrophe early after antigen encounter. BATF, together with IRF4 and Jun proteins, binds to and promotes early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors, while paradoxically repressing genes encoding effector molecules (IFNg and granzyme B). Thus, BATF amplifies TCR-dependent transcription factor expression and augments inflammatory signal propagation but restrains effector gene expression. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved.
Publication Title
The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Affymetrix Microarrays were used to analyse gene expression in aortas and circulating CD115+ cells of ApoE- and ApoE/Lymphotoxin beta receptor (LTbR)-double-deficent mice fed a Western diet from 8 to 12 weeks of age in order to identify regulated genes and pathways leading to reduced atherosclerosis in ApoE-/-/LTbR-/- mice compared to ApoE-/- littermate controls.
Publication Title
Deficiency in lymphotoxin β receptor protects from atherosclerosis in apoE-deficient mice.
Sample Metadata Fields
Sex, Age
View Samples- Macaca mulatta, Cercocebus atys
- 61 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Natural SIV infection of sooty mangabeys (SMs) does not progress to disease despite chronic virus replication. In contrast to pathogenic SIV infection of rhesus macaques (RMs), chronic SIV infection of SMs is characterized by low immune activation. To elucidate the mechanisms underlying this phenotype, we longitudinally assessed host gene expression in SIV-infected SMs and RMs. We found that acute SIV infection of SMs is consistently associated with a robust innate immune response, including widespread up-regulation of interferon-stimulated genes (ISGs). Our findings indicate that active immune regulatory mechanisms, rather than intrinsically attenuated innate immune responses, underlie the low immuneactivation of chronically SIV-infected SMs.
Publication Title
Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys.
Sample Metadata Fields
Sex, Specimen part
View Samples- Macaca mulatta, Cercocebus atys
- 15 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Transcriptional Profiling Reveals Distinguishing Features of Immune Activation in the Lymphatic Tissues of Sooty Mangabeys and Rhesus Macaques in Early SIV Infection
Publication Title
Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 63 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Sample Metadata Fields
Age, Specimen part
View Samples