Heart failure is associated with high morbidity and mortality and its incidence increases worldwide. MicroRNAs (miRNAs) are potential markers and targets for diagnostic and therapeutic applications, respectively. We determined myocardial and circulating miRNA abundance and its changes in patients with stable and end-stage heart failure before and at different time points after mechanical unloading by a left ventricular assist device (LVAD) by small-RNA-sequencing. MiRNA changes in failing heart tissues partially resembled that of fetal myocardium. Consistent with prototypical miRNA–target-mRNA interactions, target mRNA levels were negatively correlated to changes in abundance for highly expressed miRNAs in heart failure and fetal hearts. The circulating small RNA profile was dominated by miRNAs, and fragments of tRNAs and small cytoplasmic RNAs. Heart- and muscle-specific circulating miRNAs (myomirs) increased up to 140-fold in advanced heart failure, which coincided with a similar increase in cardiac troponin I protein, the established marker for heart injury. These extracellular changes nearly completely reversed 3 months following initiation of LVAD support. In stable heart failure, circulating miRNAs showed less than 5-fold differences compared to normal, and myomir and cardiac troponin I levels were only captured near the detection limit. These findings provide the underpinning for miRNA-based therapies and emphasize the usefulness of circulating miRNAs as biomarkers for heart injury performing similar to established diagnostic protein biomarkers. Overall design: Total RNA isolated from human left ventricular myocardium of failing hearts due to dilated or ischemic cardiomyopathy before and after mechanical unloading by a left ventricular assist device, and fetal myocardium compared to non-failing postnatal myocardium was subjected to multiplexed small RNA-sequencing on the Illumina platform. mRNA gene expression data using Illumina HumanHT-12v4 beadarrays for a subset of the myocardial samples is available (GSE52601).
Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers.
No sample metadata fields
View SamplesTo identify proteins regulated by glucose through changes in their rate of protein synthesis, translational profiling of MIN6 cells acutely incubated at either low or high glucose concentration was performed (i.e. microarray analysis was performed on mRNAs associated with polysomes, as an increase in the association of mRNA with polysomes is indicative of an increase in the rate of initiation step of translation and hence an increase in protein expression) (Johannes et al., 1999; Mikulits et al., 2000).
Distinct glucose-dependent stress responses revealed by translational profiling in pancreatic beta-cells.
Specimen part, Cell line, Compound, Time
View SamplesInfertility in lactating dairy cows is explained partially by the metabolic state associated with high milk production. The hypothesis was that lactating and non-lactating cows would differ in endometrial and placental transcriptomes during early pregnancy (day 28 to 42) and this difference would explain the predisposition for lactating cows to have embryonic loss at that time. Cows were either milked or not milked after calving. Reproductive [endometrium (caruncular and intercarunclar) and placenta] and liver tissues were collected on day 28, 35, and 42 of pregnancy. The primary hypothesis was rejected because no effect of lactation on mRNA abundance within reproductive tissues was found. Large differences within liver demonstrated the utility of the model to test an effect of lactation on tissue gene expression. Major changes in gene expression in reproductive tissues across time were found. Greater activation of the transcriptome for the recruitment and activation of macrophages was found in the endometrium and placenta. Changes in glucose metabolism between day 28 and 42 included greater mRNA abundance of rate-limiting genes for gluconeogenesis in intercaruncular endometrium and evidence for the establishment of aerobic glycolysis (Warburg effect) in the placenta. Temporal changes were predicted to be controlled by CSF1, PDGFB, and JUN. Production of nitric oxide and reactive oxygen species by macrophages was a mechanism to promote angiogenesis in the endometrium. Reported differences in pregnancy development for lactating versus non-lactating cows could be explained by systemic glucose availability to the conceptus and appear to be independent of the endometrial and placental transcriptomes.
The transcriptome of the endometrium and placenta is associated with pregnancy development but not lactation status in dairy cows.
Specimen part
View SamplesThe goal of this study was to identify potential AMH-induced genes and regulatory networks controlling regression by RNA-Seq transcriptome analysis of differences in Müllerian Duct mesenchyme between males (AMH signaling on) and females (AMH signaling off) in purified fetal Müllerian Duct mesenchymal cells. This analysis found 82 genes up-regulated in males during MD regression and identified Osterix (Osx)/Sp7, a key transcriptional regulator of osteoblast differentiation and bone formation, as a novel downstream effector of AMH signaling during MD regression. Overall design: Müllerian Duct mesenchymal cells mRNA profiles from 2-7 embryonic day 14.5 embryos were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.
<i>Osterix</i> functions downstream of anti-Müllerian hormone signaling to regulate Müllerian duct regression.
Sex, Specimen part, Cell line, Subject
View SamplesTransgenic Arabidopsis plants with constitutively low inositol (1,4,5) triphosphate exhibit an increased tolerance to water stress by an ABA-independent pathway
Transgenic Arabidopsis plants expressing the type 1 inositol 5-phosphatase exhibit increased drought tolerance and altered abscisic acid signaling.
No sample metadata fields
View SamplesMedroxyprogesterone acetate (MPA) is a progestin that can bind to and activate progesterone, androgen and glucocorticoid receptors. However, it is not known which receptor mediates MPA action in a cellular context where all three of these receptors are co-expressed and functional.
Anti-proliferative transcriptional effects of medroxyprogesterone acetate in estrogen receptor positive breast cancer cells are predominantly mediated by the progesterone receptor.
Cell line, Treatment
View SamplesHomeostatic hematopoietice stem cells (HSCs) with greater divisional history lose repopulating potential after very few cell divisions. Divisional history overrides both phenotype and immediate quiescence in determining functional activity. In GFP label retaining system GFP is progressively diluted when cells proceed through a cascade of divisions.
Divisional history and hematopoietic stem cell function during homeostasis.
Specimen part
View SamplesHuman embryonic stem cells (hESCs) replicate by the process of self-renewal, whilst maintaining their pluripotency. Understanding the pathways involved in the regulation of this self-renewal process will assist in developing fully-defined conditions for the proliferation of hESCS required for therapeutic applications. We previously demonstrated a role for Sphingosine-1-phosphate (S1P) in the survival and proliferation of hESCs. The present study investigates further key signalling pathways and the downstream targets of S1P.
Sphingosine-1-phosphate mediates transcriptional regulation of key targets associated with survival, proliferation, and pluripotency in human embryonic stem cells.
No sample metadata fields
View SamplesAcross life neural stem cells (NSCs) generate new neurons in the mammalian brain through asymmetric neurogenic and self-renewing cell divisions. However, the cellular mechanisms underlying NSC asymmetry remain unknown. Using fluorescence loss in photobleaching (FLIP) we here show that NSCs in vitro and within the developing forebrain generate a lateral diffusion barrier during cell division resulting in asymmetric segregation of cellular components. The strength of the diffusion barrier is dynamically regulated with age and depends on the proper function of lamin-associated nuclear envelope constituents. Strikingly, age-associated or experimental impairment of the diffusion barrier disrupts asymmetric segregation of damaged proteins, a product of aging. Thus, the data presented here identify a mechanism how age is asymmetrically distributed during somatic stem cell division.
A mechanism for the segregation of age in mammalian neural stem cells.
Age, Specimen part
View SamplesPQBP1 is a highly conserved protein closely related to neurodegenerative disorders. We identified PQBP1 as an important alternative splicing effector necessary for maintaining normal neuron functions in the brain. In order to explore PQBP1''s functions in alternative splicing regulation and neuronal activities, we systematically profiled the alternative splicing targets of PQBP1 in mouse embryonic cortical neurons by RNA-seq. The mRNAs whose alternative splicing are affected by PQBP1 showed tissue-specific functional enrichment especially in neurite outgrowth, with strong Gene Ontology (GO) enrichments for neuron projection development/morphogenesis, dendrite development and axonogenesis. PQBP1''s alternative splicing targets are also functionally enriched in RNA splicing, chromatin modification, and ARF signal transduction. Overall design: We applied RNA-seq to compare the transcriptomes of mock and PQBP1 knockdown mouse embryonic cortical neuron samples.
PQBP1, a factor linked to intellectual disability, affects alternative splicing associated with neurite outgrowth.
Cell line, Subject
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