Thrombospondin 1 (TSP-1) is an anti-angiogenic matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and gene microarray analyses on a mouse model of induced colitis.
Thrombospondin-1 type 1 repeats in a model of inflammatory bowel disease: transcript profile and therapeutic effects.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
Specimen part
View SamplesIn this study, we compared the genome-wide transcriptome of mouse and human placentas across gestation to identify species-specific signatures of early development. We also compared human placental signatures to purified primary cytotrophoblasts (CTB) isolated from placentae at different gestational age.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
No sample metadata fields
View SamplesIn this study, we compared the genome-wide transcriptome of mouse and human placentas across gestation to identify species-specific signatures of early development. We also compared human placental signatures to purified primary cytotrophoblasts (CTB) isolated from placentae at different gestational age.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
No sample metadata fields
View SamplesIn this study we identified that Sirt1 is important for mouse trophoblast stem cell (TSC) differentiation. The transcriptome of wild-type and Sirt1-null TSC were analyzed to identify dysregulation of signaling pathways.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
No sample metadata fields
View SamplesGene expression levels are determined by the balance between rates of mRNA transcription and decay, and genetic variation in either of these processes can result in heritable differences in transcript abundance. Although the genetics of gene expression has been the subject of intense interest, the contribution of heritable variation in mRNA decay rates to gene expression variation has received far less attention. To this end, we developed a novel statistical framework and measured allele-specific differences in mRNA decay rates in a diploid yeast hybrid created by mating two genetically diverse parental strains. In total, we estimate that 31% of genes exhibit allelic differences in mRNA decay rate, of which 350 can be identified at a false discovery rate of 10%. Genes with significant allele-specific differences in mRNA decay rate have higher levels of polymorphism compared to other genes, with all gene regions contributing to allelic differences in mRNA decay rate. Strikingly, we find widespread evidence for compensatory evolution, such that variants influencing transcriptional initiation and decay having opposite effects, suggesting steady-state gene expression levels are subject to pervasive stabilizing selection. Our results demonstrate that heritable differences in mRNA decay rates are widespread, and are an important target for natural selection to maintain or fine-tune steady-state gene expression levels. Overall design: We measured rates of allele-specific mRNA decay (ASD) in a diploid yeast produced by mating two genetically diverse haploid Saccharomyces cerevisiae strains: the laboratory strain BY4716 (BY), which is isogenic to the reference sequence strain S288C, and the wild Californian vineyard strain RM11-1a (RM). Briefly, we introduced rpb1-1, a temperature sensitive mutation in an RNA polymerase II subunit, to each of the haploid yeast strains, mated the strains, and grew the resulting hybrid diploid to mid-log phase at 24 °C, before rapidly shifting the culture to 37 °C to inhibit transcription. RNA-seq was performed on culture samples taken at 0, 6, 12, 18, 24, and 42 minutes subsequent to the temperature shift. To identify ASD, we used transcribed polymorphisms to distinguish between parental transcripts, and compared the relative levels of transcript abundance over the time course. Note, this experimental design internally controls for trans-acting regulatory variation as well as environmental factors. Under the null hypothesis of no ASD, the proportion of reads from the BY transcript (p_BY = N_BY / (N_BY + N_RM)) observed over the time course remains unchanged. However, genes with ASD will exhibit an increasing or decreasing proportion of BY reads as a function of time. In total, we measured ASD from three independent biological replicates.
Heritable variation of mRNA decay rates in yeast.
Disease, Cell line, Subject
View SamplesThe goal of the study was to identify transcriptional correlates of SLE disease activity both at the cohort and at the individual levels. To do so, we longitudinally profiled the whole blood transcriptomes of 158 SLE patients by microarray for up to 4 years, yielding 924 SLE samples and 48 matched pediatric healthy samples. The transcriptional data are complemented by demographic, laboratory and clinical data.
Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Race, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.
Specimen part
View SamplesMouse genetic crosses were established between the PyMT model of metastatic breast cancer and MOLF/Ei strain. Tumors were harvested from the animals for gene expression analysis to identify genes associated with progression to distant metastatic disease.
Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.
Specimen part
View SamplesMouse genetic crosses were established between the PyMT model of metastatic breast cancer and the G5 generation of the Diversity Outcross (DO). Tumors were harvested from the animals for gene expression analysis to identify genes associated with progression to distant metastatic disease.
Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.
Specimen part
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