Purpose: The goals of this study are to compare transcriptome profiling (RNA-seq) resulting from the knockout of Hira in undifferentiated mouse embryonic stem cells (mESCs) and in day 15 differentiated cardiomyocytes.Methods: RNA extraction was done in duplicate from WT and Hira-null mESCs at day0 and day15 using TRIzol reagent. RNAseq was done onIllumina Nextseq500 and processed by the ICH genomics facility, reads were aligned and normalised using BOWTIE and DEseq R2 package. Gene lists were filtered using adjusted p-value = 0.05 and absolute fold change = 2. Results:We identified 1680 transcripts changed in the absence of HIRA in day 15 differentiated cardiomyocytes. GO term cardiovascular system development was the most downregulated gene set(p-value = 0.01 and FDR =0.1. Conclusion: this study analysis the role of HIRA in early cardiac mesoderm development usinf an invitro mESCs model. Overall design: mRNA profile of WT(control) and Hira-null (KO) undifferentiated mESCs and mESCs- derived cardiomyocytes at day15 were generated by deep sequencing in duplicates using Illumina Nextseq 500 platform.
HIRA directly targets the enhancers of selected cardiac transcription factors during in vitro differentiation of mouse embryonic stem cells.
Cell line, Subject
View SamplesExpression analysis of genes potentially regulated by BMPRII and beta-catenin. BMPRII has been linked as a genetic factor to the disease pulmonary arterial hypertension.
Disruption of PPARγ/β-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival.
Specimen part
View SamplesDevelopmental transitions can be described in terms of morphology and individual genes expression patterns, but also in terms of global transcriptional and epigenetic changes. Most of the large-scale studies of such transitions, however, have only been possible in synchronized cell culture systems. Here we generate a cell type specific transcriptome of an adult stem-cell lineage in the Arabidopsis leaf using RNA sequencing and microarrays. RNA profiles of stomatal entry, commitment, and differentiating cells, as well as of mature stomata and the entire aerial epidermis give a comprehensive view of the developmental progression.
Transcriptome dynamics of the stomatal lineage: birth, amplification, and termination of a self-renewing population.
Specimen part
View SamplesDevelopmental transitions can be described in terms of morphology and individual genes expression patterns, but also in terms of global transcriptional and epigenetic changes. Most of the large-scale studies of such transitions, however, have only been possible in synchronized cell culture systems. Here we generate a cell type specific transcriptome of an adult stem-cell lineage in the Arabidopsis leaf using RNA sequencing and microarrays. RNA profiles of stomatal entry, commitment, and differentiating cells, as well as of mature stomata and the entire aerial epidermis give a comprehensive view of the developmental progression.
Transcriptome dynamics of the stomatal lineage: birth, amplification, and termination of a self-renewing population.
Specimen part
View SamplesTo understand molecular mechanisms underlying the synergy of Rb loss and E2F8 loss, we used gene expression profiling to assess molecular changes in Mx1-Cre-mediated knockout (KO) mice using RNA isolated from sorted Ter119+CD71high Erythroblasts.
Inactivation of Rb and E2f8 synergizes to trigger stressed DNA replication during erythroid terminal differentiation.
Specimen part
View SamplesVitamin D deficiency has been associated with increased esophageal cancer risk. Vitamin D controls many downstream regulators of cellular processes including proliferation, apoptosis, and differentiation. We evaluated the effects of vitamin D supplementation on global gene expression in patients with Barrett's esophagus.
A nonrandomized trial of vitamin D supplementation for Barrett's esophagus.
Specimen part
View SamplesBacterial infections cause exaserbations in COPD. Study conducted to asses the effect of Nemiralisib, a PI3Kdelta inhibitor, on S. pneumoniae infected mice
PI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner.
Specimen part, Time
View SamplesMechanical cues influence the shape, growth, and function of tissues and organs and are necessary for the development of engineered tissues. Yet, how cells sense mechanical cues and transduce them into changes in gene expression is not well understood. It is known that mechanical forces transmitted to the nucleus induce chromatin remodeling, promote DNA repair, contribute to the motion of intranuclear organelles and cause direct dissociation of protein complexes inside nuclei. Yet, the extent to which such signals impact gene expression is not understood. Because mechanical forces from the cytoskeleton to the nucleus interior are transmitted by the LINC (linker of nucleoskeleton-to-cytoskeleton) complex, we disrupted the LINC complex and performed genome wide expression studies using RNA sequencing. LINC disruption altered the expression of hundreds of genes at a genome-wide scale. We asked how LINC disruption affected the mechanosensitivity of individual genes by quantifying fold changes in gene expression on soft and stiff substrates. Remarkably, LINC disruption tended to preserve gene mechanosensitivity, but to reverse its direction. LINC disruption did not cause changes in nuclear shape, nor eliminated nuclear shape sensitivity to substrate rigidity. Our results show for the first time that the LINC complex regulates mechano-sensing at a genome-wide level, and argue for a distinct mechanism that does not require changes in nuclear morphology. Overall design: mRNA profiles of NIH 3T3 TetON cells that were induced to express either SS-GFP-KDEL (control) or SS-HA-Sun1L-KDEL by the addition of doxycycline. Two (2) substrate stiffnesses were used (1 kPa and 308 kPa), Y27632 or blebbistatin was used for certain samples to inhibit myosin II activity. A total of 6x3 reps= 18 samples were analyzed.
The mammalian LINC complex regulates genome transcriptional responses to substrate rigidity.
Cell line, Subject
View SamplesThe mammary gland at early stages of pregnancy undergoes fast cell proliferation, yet the mechanism to ensure its genome integrity is largely unknown. Here we show that pregnancy enhances expression of genes involved in numerous pathways, including most genes encoding replisomes. In mouse mammary glands, replisome genes are positively regulated by estrogen/ERa signaling but negatively regulated by BRCA1. Upon DNA damage, BRCA1 deficiency markedly enhances DNA replication initiation. BRCA1 deficiency also preferably impairs DNA replication checkpoints mediated by ATR and CHK1 but not by WEE1, which inhibits DNA replication initiation through CDC7-MCM2 pathway and enables BRCA1-deficient cells to avoid further genomic instability. Thus, BRCA1 and WEE1 inhibit DNA replication initiation in a parallel manner to ensure genome stability for mammary gland development during pregnancy.
BRCA1 represses DNA replication initiation through antagonizing estrogen signaling and maintains genome stability in parallel with WEE1-MCM2 signaling during pregnancy.
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View SamplesWe synthesized the PAX8-NFE2L2 fusion transcript and cloned it into a lentiviral vector, and used this to overexpress it in the murine prostate adenocarcinoma cell line TRAMP-C1. Overall design: We used high coverage RNA sequencing (>30 million reads per sample) to compare the expression profiles of cells expressing the PAX8-NFE2L2 fusion transcript to cells transduced with an empty vector.
Global analysis of somatic structural genomic alterations and their impact on gene expression in diverse human cancers.
Specimen part, Cell line, Subject
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