INTRODUCTION:
Increased placental expression and maternal serum levels of apoptosis-inducing TRAIL in recurrent miscarriage.
Specimen part
View SamplesData on the temporal dynamics of human placental gene expression is scarce. We have completed the first whole-genome profiling of human placental gene expression dynamics (GeneChips, Affymetrix) from early to mid- gestation (10 samples; gestational weeks 5 to 18) and report 154 genes with considerable change in transcript levels (FDR P<0.1). Functional enrichment analysis revealed >200 GO categories that are statistically over-represented among 105 genes with dynamically increasing transcript levels. Analysis in an extended sample (n=43; gestational weeks 5 to 41) conformed a highly significant (FDR P<0.05) expressional peak in mid-gestation placenta for ten genes: BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10, STC1. A central hypothesis of our study states that the aberrant expression of genes characteristic to mid-gestation placenta may contribute to affected fetal growth, maternal preeclampsia (PE) or gestational diabetes (GD). The gene STC1 coding for Stanniocalcin 1 (STC1) was identified with a sharp placental expressional peak in mid-gestation, increased mRNA levels at term and significantly elevated STC1 protein levels in post-partum maternal plasma in all pregnancy complications. The highest STC1 levels were identified in women, who developed simultaneously PE and delivered an SGA baby (median 731 vs 418 pg/ml in controls; P=0.001). CCNG2 and LYPD6 exhibited significantly increased placental mRNA expression and enhanced intensity of immunohistochemistry staining in placental sections all studied in GD and PE cases. Aberrant expression of mid-gestation specific genes in pregnancy complications at term indicates the importance of the fine-scale tuning of the temporal dynamics of transcription regulation in placenta. Observed significantly elevated plasma STC1 in complicated pregnancies warrants further investigations of its potential as a biomarker. Interestingly, a majority of genes with high expression in mid-gestation placenta have also been implicated in adult complex disease. This observation promotes a recently opened discussion on the role of placenta in developmental programming.
Mid-gestational gene expression profile in placenta and link to pregnancy complications.
Specimen part
View SamplesFor up to 70 weeks we subcutaneuously injected two hundered p53R270HWAPCre mice to different insulin-like molecules (regular insulin, insulin glargine, insulin X10 (of AspB10), IGF1 or vehicle solution). Due to the mammary gland specific p53 mutation the p53R270HWAPCre mice will develop spontanously human like mammary gland tumors in about a year. We found that frequent injections to insulin like molecules decreased the mammary gland tumor latency time in this model. Next we mRNA seqeunced tumors to reveal the underlying mechanisms for the increased tumor progression. For the next generation experiment we isolated mRNA from 50 tumors (10 tumors of each stimulation group) and sequenced with the IonTorrent (40 mil reads, on average 100 bp reads) Overall design: RNA expression profiles of 50 mammary gland tumors were analyzed, 10 tumors per treatment group (chronic insulin, glargine, x10, IGF1 or vehicle exposure)
Insulin-like growth factor 1 receptor activation promotes mammary gland tumor development by increasing glycolysis and promoting biomass production.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sex, Specimen part
View SamplesTo unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis.
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sex, Specimen part
View SamplesTo unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis.
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sex, Specimen part
View SamplesTo unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis.
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sex, Specimen part
View SamplesTo unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis.
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sex, Specimen part
View SamplesPurpose: Here we describe the modulation of a gene expression program involved in cell fate. Methods: We depleted U2AF1 in human induced pluripotent stem cells (hiPSCs) to the level found in differentiated cells using an inducible shRNA system, followed by high-throughput RNAseq, revealing a gene expression program involved in cell fate determination. Results: Approximately 85% of the total raw reads were mapped to the human genome sequence (GRCh37), giving an average of 200 million human reads per sample for total RNA and 15 million human reads per sample for small RNA libraries. Conclusions: Our results show that transcriptional control of gene expression in hiPSCs can be set by the CSF U2AF1, establishing a direct link between transcription and AS during cell fate determination. Overall design: hiPSCs were differentiated into the three germ layers following the described protocol in the study (Gifford et al., 2013).
The core spliceosomal factor U2AF1 controls cell-fate determination via the modulation of transcriptional networks.
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View SamplesRationale: VEGF family members mediate their effects through cell surface receptors VEGFR-1, VEGFR-2 and NRP. Specific ligands were used to stimulate specific combinations of the receptors to evaluate ligand and receptor properties. Objective: The properties of a novel VEGF family member Vammin were studied in level of receptor binding, gene expression in HUVECs by RNAseq and in vivo using adenoviral gene trasfers. Methods: HUVECs were trasduced using adenoviral vectors encoding VEGF-A109, VEGF-A165 and Vammin and with an empty vector as a control. Gene expression was measured using RNA sequencing. Adenoviral intramuscular gene transfers were performed into rabbit hindlimbs. Confocal and multiphoton microscopy were used for blood vessel imaging. Results and conclusions: Vammin is a highly effective VEGFR2 ligand that induces differential gene expression of genes related to proliferation, survival, angiogenesis and blood vessel development in HUVECs. The effect is stronger than ones induced by VEGF-A165 and VEGF-A109. Vammin induces highly efficient angiogenic responses when delivered into rabbit skeletal muscles using adenoviral gene transfers. Overall design: HUVEC mRNA profiles after adenoviral vector gene transfers in duplicate.
Snake venom VEGF Vammin induces a highly efficient angiogenic response in skeletal muscle via VEGFR-2/NRP specific signaling.
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