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SRP073200
Mus musculus
9 Downloadable Samples
Illumina HiSeq 2500
Description
Networks of coordinated alternative splicing (AS) events play critical roles in development and disease. However, a comprehensive knowledge of the factors that regulate these networks is lacking. We describe a high-throughput system for systematically linking trans-acting factors to endogenous RNA regulation events. Using this system, we identify hundreds of factors associated with diverse regulatory layers that positively or negatively control AS events linked to cell fate. Remarkably, more than one third of the new regulators are transcription factors. Further analyses of the zinc finger protein Zfp871 and BTB/POZ domain transcription factor Nacc1, which regulate neural and stem cell AS programs, respectively, reveal roles in controlling the expression of specific splicing regulators. Surprisingly, these proteins also appear to regulate target AS programs via binding RNA. Our results thus uncover a large ‘missing cache’ of splicing regulators among annotated transcription factors, some of which dually regulate AS through direct and indirect mechanisms. Overall design: RNA-Seq of N2A cells upon RNAi-mediated knockdown of Mbnl1/Mbnl2 or Nacc1, or control knockdown (1 replicate each), as well as upon knockdown of Srrm4 or Zfp871, or control knockdown (2 replicates each) vast-tools.AltSplicing_Mbnl.Nacc1.tab: Primary vast-tools output for Mbnl and Nacc1 knockdowns vast-tools.AltSplicing_Srrm4.Zfp871.tab: Primary vast-tools output for Srrm4 and Zfp871 knockdowns AltSplicing_Mbnl.Nacc1.tab: Filtered PSI values and differential AS annotation for Mbnl and Nacc1 knockdowns AltSplicing_Srrm4.Zfp871.tab: Filtered PSI values and differential AS annotation for Srrm4 and Zfp871 knockdowns Expression_Mbnl.Nacc1.tab: Raw and read counts per gene, normalized expression and fold-change for Mbnl and Nacc1 knockdowns Expression_Srrm4.Zfp871.tab: Raw read counts per gene, normalized expression and fold-change (edgeR analysis) for Srrm4 and Zfp871 knockdowns
Publication Title
Multilayered Control of Alternative Splicing Regulatory Networks by Transcription Factors.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina HiSeq 2500
Description
AGRP neurons are a hypothalamic population that senses physiological energy deficit and consequently increases appetite. Molecular and cellular processes for energy-sensing and elevated neuronal output are critical for understanding the central nervous system response to energy deficit states, such as during weight-loss. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss but, in adult mice, this has been limited by technical challenges. We report high-quality gene expression profiles of AGRP neurons under well-fed and energy deficit states. For comparison, we also analyzed POMC neurons, an intermingled population that suppresses appetite. This data newly identifies cell type-selective involvement of signaling pathways, ion channels, neuropeptides, and G-protein coupled receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders. Overall design: Examination of 2 different neuronal cell types under 2 conditions.
Publication Title
Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 40 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Murine healthy tissue samples, DCIS and invasive mammary tumors were analyzed in order to identify marker genes which show enhanced expresssion in DCIS and invasive ductal carcinomas.
Publication Title
Identification of early molecular markers for breast cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human healthy tissue samples, DCIS and invasive mammary tumors were analyzed in order to identify marker genes which show enhanced expresssion in DCIS and invasive ductal carcinomas.
Publication Title
Identification of early molecular markers for breast cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
we used technique that allows the molecular characterization of particular neuronal subpopulations based on their neuroanatomical projections and the locations of their cell bodies. This 'retro-TRAP' (translating ribosome affinity purification from retrogradely labeled neurons) approach relies on viral injection into an anatomical area targeted by the neurons of interest, followed by selective precipitation of ribosomes from retrogradely labeled cell bodies, and subsequent RNAseq analysis. Overall design: By comparing the mRNAs enriched in the NGC neurons which are retrogradely labeled due to viral injection into central thalamus, to gene expression of non-labeled surrounding cells in NGC, and then performing a comprehensive bioinformatics analysis of these results, we were able to identify genes enriched in these cells. This procedure allowed us to highlight genes and pathways unique to these neurons with projections ascending to thalamus, as compared to other cells in reticular NucleusGigantocellularis.
Publication Title
Molecular profiling of reticular gigantocellularis neurons indicates that eNOS modulates environmentally dependent levels of arousal.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Notch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Publication Title
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A surge of luteinizing hormone (LH) from the pituitary gland triggers ovulation, oocyte maturation, and luteinization for successful reproduction in mammals. Since the signaling molecules RAS and ERK1/2 are activated by a LH surge in granulosa cells of preovulatory follicles, we disrupted Erk1/2 in mouse granulosa cells and provide in vivo evidence that these kinases are necessary for LH-induced oocyte resumption of meiosis, ovulation, and luteinization. In addition, biochemical analyses and selected disruption of the Cebpb gene in granulosa cells demonstrate that C/EBP is a critical downstream mediator of ERK1/2 activation. These mouse models provide in vivo systems in which to define the context specific and molecular mechanisms by which granulosa cells respond to LH and these mechanisms are relevant to the regulation of human fertility and infertility.
Publication Title
MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 44 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective Tissue Growth Factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. To test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase C (PKC) mouse model of DCM. Transgenic mice expressing constitutively active PKC in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to heart failure, cardiac fibrosis, and increased mortality. Beginning at 3 months of age, mice were treated with an antibody to CTGF (FG-3149) or non-immune IgG control antibody for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic function in PKC mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling were elevated in PKC mice, but significantly decreased by CTGF inhibition, however total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKC mice suggests that CTGF inhibition may benefit patients with DCM.
Publication Title
Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Danio rerio
- 30 Downloadable Samples
- IlluminaHiSeq2500
Description
Endogenous oligodendrocyte progenitor cells (OPCs) are a promising target to improve functional recovery after spinal cord injury (SCI) by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neuron. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation. Overall design: DEG analysis of primary OPC and OL populations, 5 biological replicates per population
Publication Title
Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation <i>In Vitro</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Pancreatic ductal adenocarcinoma (PDA) is characterized by abundant desmoplasia and poor tissue perfusion. These features are proposed to limit access of therapies to neoplastic cells and blunt treatment efficacy. Indeed, several agents that target the PDA microenvironment promote chemotherapy delivery and improve anti-neoplastic responses in murine models of PDA. Here, we employed the FG-3019 monoclonal antibody directed against the pleiotropic matricellular signaling molecule connective tissue growth factor (CTGF/CCN2). FG-3019 treatment increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. Microarray expression profiling revealed the down-regulation by FG-3019 of several anti-apoptotic transcripts, including the master regulator Xiap, down-regulation of which has been shown to sensitize PDA to gemcitabine. Decreases in XIAP protein by FG-3019 in the presence and absence of gemcitabine were confirmed by immunoblot, while increases in XIAP protein were seen in PDA cell lines treated with recombinant CTGF. Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models and, by extension, PDA patients.
Publication Title
CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples