Aberrant splicing in livers of SRSF KO mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Nick Webster
PROVIDER: E-GEOD-57021 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:RNA from primary hepatocyte cultures from three 3-month-old SRSF1HKO mice compared to RNA from three 3-month-old WT mice for changes in exon utilization and gene expression. SRSF1 KO vs. WT, three replicates each.
2015-05-01 | E-GEOD-57020 | biostudies-arrayexpress
Project description:RNA from three hepatocellular carcinomas from 24-month-old SRSF3HKO mice compared to RNA from non-tumorous liver from 24-month-old SRSF3HKO mice for changes in exon utilization and gene expression. Liver tumor vs. normal liver, three replicates each.
2015-05-01 | E-GEOD-57019 | biostudies-arrayexpress
Project description:Background:Breast cancer is the second most frequent type of cancer affecting women. We are increasingly aware that changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specifically about the involvement of alternative splicing in the formation of macroscopic metastases. Our study investigates transcript isoform changes that characterize tumors of different abilities to form growing metastases. Results:To identify alternative splicing events (ASEs) that are associated with the fully metastatic phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic (168FARN and 4T07) and highly metastatic (4T1) mammary carcinomas. Statistical analysis identified significant expression changes in 7606 out of 155,994 (4%) exons and in 1725 out of 189,460 (1%) intronic regions, which affect 2623 out of 16,654 (16%) genes. These changes correspond to putative alternative isoforms - several of which are novel - that are differentially expressed between tumors of varying metastatic phenotypes. Gene pathway analysis showed that 1224 of genes expressing alternative isoforms were involved in cell growth, cell interactions, cell proliferation, cell migration and cell death and have been previously linked to cancers and genetic disorders. We chose ten predicted splice variants for RT-PCR validation, eight of which were successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1). These include three novel intron retentions in CD44, a gene in which isoform variations have been previously associated with the metastasis of several cancers. Conclusions:Our findings reveal that various genes are differently spliced and/or expressed in association with the metastatic phenotype of tumor cells. Identification of metastasis-specific isoforms may contribute to the development of improved breast cancer stage identification and targeted therapies. Keywords: Seek pre-mRNA changes associated with the fully metastatic phenotype in breast cancer We used RNA tumor tissues derived from three murine mammary carcinoma cell lines (168FARN, 4T07 and 4T1); four biological replicates of 168FARN, four biological replicates of 4T07, and four biological replicates of 4T1 were hybridized independently at McGill university site.
2010-06-08 | E-GEOD-21994 | biostudies-arrayexpress
Project description:The control of RNA alternative splicing is critical for generating biological diversity. Despite emerging genome-wide technologies to study RNA complexity, reliable and comprehensive RNA-regulatory networks have not been defined. Here we used Bayesian networks to probabilistically model diverse datasets and predict the target networks of specific regulators. We applied this strategy to identify ~700 alternative splicing events directly regulated by the neuron-specific factor Nova in the mouse brain, integrating RNA-binding data, splicing microarray data, Nova-binding motifs, and evolutionary signatures. The resulting integrative network revealed combinatorial regulation by Nova and the neuronal splicing factor Fox, interplay between phosphorylation and splicing, and potential links to neurologic disease. Thus we have developed a general approach to understanding mammalian RNA regulation at the systems level. RNA from the whole brain or spinal cord of 4 wild type and 4 Nova1/2 double KO (dKO) E18.5 CD1 mice. One array per biological replicate.
2010-08-04 | E-GEOD-22115 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-08-31 | E-GEOD-71707 | biostudies-arrayexpress
Project description:The 3' untranslated regions (3' UTRs) of mRNAs contain cis-acting elements for posttranscriptional regulation of gene expression. Here, we report that mouse genes tend to express mRNAs with longer 3' UTRs as embryonic development progresses. This global regulation is controlled by alternative polyadenylation and coordinates with initiation of organogenesis and aspects of embryonic development, including morphogenesis, differentiation, and proliferation. Using myogenesis of C2C12 myoblast cells as a model, we recapitulated this process in vitro and found that 3' UTR lengthening is likely caused by weakening of mRNA polyadenylation activity. Because alternative 3' UTR sequences are typically longer and have higher AU content than constitutive ones, our results suggest that lengthening of 3' UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation. Two biological replicates of C2C12 growth and differentiation conditions, repesctively
2010-08-31 | E-GEOD-23871 | biostudies-arrayexpress
Project description:To examine whether energy starvation caused by the increase in rRNA transcription affects liver metabolism, we compared the gene expression profiles of WT and NML-KO livers using Affymetrix microarray technology. We analyzed 5 livers of WT mice and 5 livers of NML-KO mice.
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Project description:Rett syndrome (RTT) is a neurodevelopmental disorder characterized by developmental regression around 6-18 months after birth, followed by a lifetime of intellectual disability, stereotyped behaviors, and motor deficits. RTT is caused by mutations in MeCP2, a methyl-CpG binding protein that was traditionally believed to repress gene expression. Gene expression studies of individual brain regions, however, have revealed that MeCP2 loss-of-function leads to the subtle activation and repression of its gene targets. However, these results may be confounded by the extensive neuronal cell heterogeneity inherent in these brain structures. To minimalize this issue of heterogeneity, we assessed whether Mecp2-null mice exhibited alterations in gene expression patterns in the striatum, a brain nucleus with relatively homogenous neuronal types and is highly relevant to the motor deficits observed in RTT. Despite the homogeneity of the tissue, the fold-change of the 127 differentially expressed genes we identified remained low with a mean change consistent with other studies. However, many of those genes differentially expressed in the striatum have not been previously identified in gene expression analyses of other brain regions. This suggests therefore that the differential expression of genes following loss of MeCP2 occurs in a tissue, or cell-type specific manner and thus MeCP2 function should be understood in a cellular context. In initiating this study, we reasoned that reducing the number of cell types in a microarray experiment may reveal transcriptional changes that are masked in a whole tissue analysis. We therefore focused on tissues more homogeneous in regards to the diversity of neuronal cell types they contain in order to discern gene expression changes in the absence of MeCP2. We chose to isolate the striatum, a tissue composed predominantly of GABAergic medium spiny neurons (MSNs). The striatum was resected from five symptomatic Mecp2-null (KO) male mice bearing the Bird allele and five wild-type (WT) littermates in a C57BL/6 background. We also isolated liver from the same individuals to serve as a non-neuronal control. RNA was isolated from these tissues, converted to cDNA, and hybridized to a single-channel Affymetrix GeneChip Mouse Exon 1.0 ST array for a total of 20 individual arrays.
2013-07-13 | E-GEOD-42895 | biostudies-arrayexpress
Project description:Myeloid derived suppressor cells (MDSCs) are an immunosuppressive population of immature myeloid cells found in advanced stage cancer patients and mouse tumor models. To identify potential genes playing essential role in MDSC biology, we have conducted microarray analysis of gene expression in MDSCs from esophageal tumor-bearing mice, compared to immature myeloid cells from healthy littermate control mice. In this dataset, we include the expression data obtained from sorted splenic CD11b+Gr1+ cells from tumor-bearing L2-Cre;p120f/f mice, compared to healthy littermate controls. Using these data, we have identified 964 genes showing differential expression between the two groups. Among these was the Cd38 gene, which was among the genes most upregulated in MDSCs from tumor-bearing mice. 9 total samples were analyzed: 6 sample from experimental tumor-bearing mice and three pooled samples from control mice. Gene expression difference was determined by univariate test (two-sample t-test) with multivariate permutation test (10,000 random permutations). A cut-off p-value of less than 0.001 and minimum 2-fold expression change were used to identify genes with significant expression differences between the two groups.
2015-08-31 | E-GEOD-71706 | biostudies-arrayexpress
Project description:Myeloid derived suppressor cells (MDSCs) are an immunosuppressive population of immature myeloid cells found in advanced stage cancer patients and mouse tumor models. We have identified Cd38 gene as potentially playing an essential role in MDSC biology. To determine the diffences between CD38high and CD38 low MDSCs from tumor-bearing mice, we have conducted this microarray. In this dataset, we include the expression data obtained from sorted splenic CD38high CD11b+Gr1+ cells from tumor-bearing L2-Cre;p120f/f mice, compared to CD38low CD11b+Gr1+ cells from the same mice. Using these data, we have detected differential expression of 498 genes . The Nos2 gene was among the genes most upregulated in CD38high MDSCs. 8 total samples were analyzed: 3 pairs of CD38high and CD38 low MDSCs (coming from individual mice), as well a pair of CD38high and CD38low pulled MSDCs (splenocytes from 3 mice were pulled together for sorting to increase yields). Gene expression difference was determined by univariate test (two-sample t-test) with multivariate permutation test (10,000 random permutations). A cut-off p-value of less than 0.001 and minimum 2-fold expression change were used to identify genes with significant expression differences between the two groups.
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