The atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV node-specific reporter mouse to gain insight into the gene programs determining the formation and phenotype of the AV node. In the transgenic reporter, green fluorescent protein (GFP) expression was driven by 160 kbp of Tbx3 and flanking sequences. GFP was selectively expressed in the AV canal of embryos, and in the AV node of adults, while all other Tbx3+ conduction system components, including the AV bundle, were devoid of GFP expression. Fluorescent AV nodal (Tbx3BAC-Egfp) and complementary working (NppaBAC336-Egfp) myocardial cell populations of E10.5 embryos and E17.5 fetuses were purified using fluorescence-activated cell sorting, and their expression profiles were assessed by microarray analysis. We constructed a comprehensive list of sodium, calcium, and potassium channels specific for the nodal or working myocard. Furthermore, the data revealed that the AV node and the working myocardium phenotypes diverge during development, but that the functional gene classes characteristic for both compartments are maintained. Interestingly, the AV node-specific gene repertoire consisted of multiple neurotrophic factors not yet appreciated to play a role in nodal development. These data present the first genome-wide transcription profiles of the AV node during development, providing valuable information concerning its molecular identity.
Gene expression profiling of the forming atrioventricular node using a novel tbx3-based node-specific transgenic reporter.
No sample metadata fields
View SamplesThree triple negative breast cancer cell lines (MDAMB231, SUM159, and HCC1806) were treated with small molecule inhibitors (JQ1, BET bromodomain inhibitor; GSK2801, BAZ2A/B bromodomain inhibitor) alone and in combination for 72 hours Overall design: 12 experimental samples
GSK2801, a BAZ2/BRD9 Bromodomain Inhibitor, Synergizes with BET Inhibitors to Induce Apoptosis in Triple-Negative Breast Cancer.
Cell line, Treatment, Subject
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
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