Cell-autonomous circadian oscillations strongly influence tissue physiology and pathophysiology of peripheral organs. Recent in vivo findings in the heart demonstrate that the circadian clock controls oscillatory gene expression programs in the adult myocardium. However, whether in vitro human embryonic stem (ES) cell-derived cardiomyocytes can establish circadian rhythmicity is unknown. Here we report that while undifferentiated human ES cells do not possess a functional clock, oscillatory expression of known core clock genes emerges during directed cardiac differentiation, with robust rhythms in day 30 cardiomyocytes. Our data reveal a stress related oscillatory network of genes that underlies a time-dependent response to doxorubicin, a frequently used anti-cancer drug with cardiotoxic side effects. These results provide a set of oscillatory genes that is relevant to functional cardiac studies and that can be deployed to uncover the potential contribution of the clock to other processes such as cardiac regeneration. Overall design: Human embryonic stem cells (ES cells) were differentiated via a directed differentiation protocol in vitro towards cardiomyocytes for a period of 30 days. Cardiomyocytes were synchronized with dexamethasone and triplicate samples for RNA extraction and sequencing were taken every 4 hours for 48 hours in total. RNA was then extracted using TRIzol, barcoded and amplified following the CEL-Seq protocol.
Circadian networks in human embryonic stem cell-derived cardiomyocytes.
Specimen part, Subject
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Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice.
Specimen part
View SamplesThe transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs.
Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice.
Specimen part
View SamplesThe transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs.
Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice.
Specimen part
View SamplesWe used microarrays to reveal the global expression profiles of young and old whole lateral ventricle choroid plexus tissue.
Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells.
Sex, Specimen part
View SamplesThe forkhead O transcription factors (FOXO) integrate a range of extracellular signals including growth factor signaling, inflammation, oxidative stress and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many cell-type specific responses yet to be unraveled. Naive antigen-specific CD8+ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure, but in addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival.
Differentiation of CD8 memory T cells depends on Foxo1.
Specimen part
View SamplesUstilago maydis is a basidiomycete fungus that causes smut disease in maize. Most prominent symptoms of the disease are plant tumors, which can be induced by U. maydis on all aerial parts of the plant. We identified two linked genes, pit1 and pit2, which are specifically expressed during plant colonization. Deletion mutants for either pit1 or pit2 are unable to induce tumor development and elicit plant defense responses.
Two linked genes encoding a secreted effector and a membrane protein are essential for Ustilago maydis-induced tumour formation.
Specimen part, Disease, Disease stage
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Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory.
Specimen part
View SamplesDuring acute viral infections, nave CD8+ T cells differentiate into effector CD8+ T cells and, after viral control, into memory CD8+ T cells. Memory CD8+ T cells are highly functional, proliferate rapidly upon reinfection and persist long-term without antigen. In contrast, during chronic infections, CD8+ T cells become exhausted and have poor effector function, express multiple inhibitory receptors, possess low proliferative capacity, and cannot persist without antigen. To compare the development of functional memory T cells with poorly functional exhausted T cells, we generated longitudinal transcriptional profiles for each.
Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory.
Specimen part
View SamplesMany of the genes coding for secreted protein effectors are arranged in gene clusters in the genome of the biotrophic plant pathogen Ustilago maydis. The largest of these gene clusters, cluster 19A, encodes 24 secreted effectors. Deletion of the entire cluster results in severe attenuation of virulence. The generation and analysis strains carrying sub-deletions identified 9 genes significantly contributing to tumor formation after seedling infection. As the individual contributions of these genes to tumor formation were small, we studied the response of maize plants to the whole cluster mutant as well as to several individual mutants by array analysis. This revealed distinct plant responses, demonstrating that the respective effectors have discrete plant targets. Many of the genes coding for secreted protein effectors are arranged in gene clusters in the genome of the biotrophic plant pathogen Ustilago maydis. The largest of these gene clusters, cluster 19A, encodes 24 secreted effectors. Deletion of the entire cluster results in severe attenuation of virulence. The generation and analysis strains carrying sub-deletions identified 9 genes significantly contributing to tumor formation after seedling infection. As the individual contributions of these genes to tumor formation were small, we studied the response of maize plants to the whole cluster mutant as well as to several individual mutants by array analysis. This revealed distinct plant responses, demonstrating that the respective effectors have discrete plant targets.
Characterization of the largest effector gene cluster of Ustilago maydis.
Specimen part, Treatment
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