The overall goal of our studies is to elucidate the cellular and molecular mechanism by which the transcription factor Casz1 functions in murine heart development. We established that Casz1 is expressed in myocardial progenitor cells beginning at E7.5 and in differentiated cardiomyocytes throughout development. We generated conditional Casz1 knockout mice to show that ablation of CASZ1 in Nkx2.5-positive cardiomyocytes leads to cardiac hypoplasia, ventricular septal defects and lethality by E13.5. To identify the pathways and networks by which Casz1 regulates cardiomyocyte development, we used RNA-Seq and identified genes involved in cell proliferation are upregulated in Casz1 mutants compared to wild-type littermates. We conclude that Casz1 is essential for cardiac development and has a pivotal role in regulating part of the cardiac transcriptional program. Overall design: 3 biological replicates of the two genotypes (Nkx2-5+/+,Casz1f/+ and Nkx2-5Cre/+,Casz1f/f) were used for RNA-seq to determine genes that are differentially expressed in the murine heart when Casz1 is mutated. Nkx2-5+/+,Casz1f/+ were used as wild-type controls for comparison.
Casz1 is required for cardiomyocyte G1-to-S phase progression during mammalian cardiac development.
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View SamplesResveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan
Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span.
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View Samples12 C57BL/6 mice were infected orogastrically with the H. pylori strain SS1. After 6 and 12 months, 3 non-infected and 3 infected mice were sacrificed and stomachs isolated. Gastric tissues were disaggregated and total RNA were isolated by TRIzol extraction and then purified on RNeasy minicolumns. After synthesis of the first cDNA strand (In vitrogen), the double-stranded cDNA was obtained and used to produce biotin-labeled cRNA (Enzo Diagnostic). FRagmented cRNA was hybridized to GeneChip Mouse expression array 430A (Affymetrix).
Interferon gamma-signature transcript profiling and IL-23 upregulation in response to Helicobacter pylori infection.
Sex, Age, Specimen part, Disease, Subject, Time
View SamplesIn rodents, the uterus of a mature
Fine temporal analysis of DHT transcriptional modulation of the ATM/Gadd45g signaling pathways in the mouse uterus.
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View Samples17-Estradiol (E2) is well known to be associated with uterine cancer, endometriosis, and leiomyomas. Although insulin-like growth factor I (IGF-I) has been identified as a mediator of the uterotrophic effect of E2 in several studies, this mechanism is still not well understood. In the present study, identification of the genes modulated by a physiological dose of E2, in the uterus, has been done in ovariectomized mice using Affymetrix microarrays. The E2-induced genomic profile shows that multiple genes belonging to the IGF-I pathway are affected after exposure to E2. Two phases of regulation could be identified. First, from 0 to 6 h, the expression of genes involved in the cell cycle, growth factors, protein tyrosine phosphatases, and MAPK phosphatases is quickly upregulated by E2, while IGF-I receptor and several genes of the MAPK and phosphatidylinositol 3-kinase pathways are downregulated. Later, i.e., from 6 to 24 h, transporters and peptidases/proteases are stimulated, whereas defense-related genes are differentially regulated by E2. Finally, cytoarchitectural genes are modulated later. The present data show that a physiological dose of E2 induces, within 24 h, a series of transcriptional events that promote the uterotrophic effect. Among these, the E2-mediated activation of the IGF-I pathway seems to play a pivotal role in the uterotrophic effect. Furthermore, the protein tyrosine phosphatases and MAPK phosphatases are likely to modulate the estrogenic uterotrophic action by targeting, at different steps, the IGF-I pathway.
Temporal analysis of E2 transcriptional induction of PTP and MKP and downregulation of IGF-I pathway key components in the mouse uterus.
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View SamplesUnder various pathophysiological muscle-wasting conditions like diabetes and starvation, a family of ubiquitin ligases, including MuRF1 (Muscle specific RING-Finger protein 1), are induced to target muscle proteins for degradation via ubiquitination. In an attempt to identify the in vivo targets of MuRF1 we have generated transgenic mouse lines overexpressing MuRF1 in a skeletal muscle specific fashion. MuRF1-TG lines were viable and had normal fertility. Characterization of their skeletal muscles did not reveal evidence for muscle wasting at 10 weeks of age. In this experiment we compared the skeletal muscle transcriptome of transgenic mice with wildtypes.
MuRF1-dependent regulation of systemic carbohydrate metabolism as revealed from transgenic mouse studies.
Sex, Age, Specimen part
View SamplesThe response of bacteria to the conditions at the site of infection is a key part of the transcriptional program that will determine the sucess of the infectious agent. To model the environment of the distal airway, we used bovine pulmonary surfactant (Survanta). P. aeruginosa transcript levels were measured in the presence or absence of Survanta in MOPS minimal medium to identify transcripts altered in response to surfactant. The most highly induced transcript in Survanta was PA5325, renamed sphA based on our findings that the gene was specifically induced by sphingosine derived from the sphingomyelin present in pulmonary surfactant. A divergently transcribed transcription factor, PA5324, was demonstrated to be critical for the sphingosine dependent induction of sphA and was therefore renamed SphR. Microarrays of the sphR mutant cells were compared to wild type to determine the likely SphR regulon.
Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.
Treatment
View SamplesDespite 20 years since its discovery, the gene responsible for Huntington’s Disease, HTT, has still not had its function or transcriptional profile completely characterized. In response to a recent report by Ruzo et al. of several novel splice forms of HTT in human embryonic stem cell lines, we have analyzed a set of mRNA sequencing datasets from post mortem human brain from Huntington’s disease, Parkinson’s disease, and neurologically normal control subjects to evaluate support for previously observed and to identify novel splice patterns. A custom analysis pipeline produced supporting evidence for some of the results reported by two previous studies of alternative isoforms as well as identifying previously unreported splice patterns. All of the alternative splice patterns were of relatively low abundance compared to the canonical splice form. Overall design: 29 Huntington''s Disease, 29 Parkinson''s Disease, and 50 Neurologically normal control samples from human post-mortem prefrontal cortex
Evidence of Extensive Alternative Splicing in Post Mortem Human Brain HTT Transcription by mRNA Sequencing.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrating factor analysis and a transgenic mouse model to reveal a peripheral blood predictor of breast tumors.
Specimen part
View SamplesWe analyzed gene expression in human peripheral blood mononuclear cells (PBMCs) from breast cancer patients, patients with benign breast abnormalities, healthy cancer-free individuals as well as patients with other types of cancer (gastrointestinal and brain cancers).
Integrating factor analysis and a transgenic mouse model to reveal a peripheral blood predictor of breast tumors.
Specimen part
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