Controlled activation of epidermal growth factor receptor (EGFR) is systematically guaranteed at the molecular level, however aberrant activation of EGFR is frequently found in cancer. Transcription induced by EGFR activation often involves coordinated expression of genes that positively and negatively regulate the original signaling pathway, therefore alterations in EGFR kinase activity may reflect changes in gene expression associated with the pathway. In this study, we investigated transcriptional changes following EGF stimulation with or without the EGFR kinase inhibitor Iressa in H1299 human non-small-cell lung cancer cells (parental H1299, H1299 cells which overexpress wild-type: EGFR-WT and mutant EGFR: L858R). Our results clearly showed differences in transcriptional activity in the absence or presence of EGFR kinase activity, and genes sharing the same molecular functions showed distinct expression dynamics. The results showed particular enrichment of EGFR/ErbB signaling-related genes in a differentially expressed gene set, and significant protein expression of MIG6/RALT(ERRFI1), an EGFR negative regulator, was confirmed in L858R. High MIG6 protein expression was correlated with basal EGFR phosphorylation and inversely correlated with EGF-induced ERK phosphorylation levels. Investigation of NCI-60 cell lines showed that ERRFI1 expression was correlated with EGFR expression regardless of tissue type. These results suggest that cells accumulate MIG6 as an inherent negative regulator to suppress excess EGFR activity when basal EGFR kinase activity is considerably high. Taken together, an EGFR mutation can cause transcriptional changes to accommodate the activation potency of the original signaling pathway at the cellular level.
Mutation of epidermal growth factor receptor is associated with MIG6 expression.
Cell line
View SamplesNeonatal germ cell development provides the foundation of spermatogenesis. However, a systematic understanding of this process is still limited. To resolve the cellular and molecular heterogeneity, we profiled single-cell transcriptomes of undifferentiated germ cells from neonatal mouse testes and employed unbiased clustering and pseudotime ordering analysis to assign cells to distinct cell states in the developmental continuum. We defined the unique transcriptional programs underlying the migratory capacity, resting cellular states and apoptosis regulation in transitional gonocytes. We also identified a subpopulation of primitive spermatogonia marked by CD87/uPAR, which exhibited a higher level of self-renewal gene expression and migration potential. We further revealed a differentiation-primed state within the undifferentiated compartment, in which elevated Oct4 expression correlates with lower expression of self-renewal pathway, higher Rarg expression, and enhanced retinoic acid responsiveness. Lastly, the knockdown experiment revealed the role of Oct4 in the regulation of gene expression related to the MAPK pathway and cell adhesion, which may contribute to stem cell differentiation. Our study thus provides novel insights into the cellular and molecular regulations during early germ cell development. Overall design: Here, we performed single-cell RNA-Seq of germ cells from mouse testes on postnatal day (PND) 5.5. We also obtained transcriptomes of subpopulations marked by different levels of CD87 or Oct4-GFP, as well as SSC culture after Oct4 knockdown by bulk RNA-Seq.
Revealing cellular and molecular transitions in neonatal germ cell differentiation using single cell RNA sequencing.
Sex, Specimen part, Subject
View SamplesPrimary neonatal cardiomyocytes treated with human cardiotrophin 1 (hCT1) or control (Ctrl) for 24 hours
Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart.
Specimen part
View SamplesAnalysis of umbilical vein endothelial cells (HUVEC) treated with Egr-3 siRNA under the VEGF treatment for 0,1, and 4 h. Egr-3, a member of early growth response family, is immediately and dramatically induced by VEGF in HUVEC, which regulates expression of many genes related to endothelial activation.
Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3.
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View SamplesStem samples of wildtype Columbia plants and the wox4-1 mutant (Gabi_462G01) were analyzed in order to draw a connection between general transcriptomic changes during interfascicular formation in the wildtype and WOX4-dependent gene regulation during this process.
WOX4 imparts auxin responsiveness to cambium cells in Arabidopsis.
Specimen part
View SamplesIn-vivo induced establishment and activity of the interfascicular cambium in Arabidopsis thaliana stems under NPA treatments.
WOX4 imparts auxin responsiveness to cambium cells in Arabidopsis.
Specimen part, Treatment
View SamplesHuR-deficient cells showed the decreased expression of genes involved in chemotaxis, cell proliferation and signal transduction.
Hu Antigen R Regulates Antiviral Innate Immune Responses through the Stabilization of mRNA for Polo-like Kinase 2.
Specimen part, Cell line
View SamplesEVI1 is one of the famous poor prognostic markers for a chemotherapy-resistant acute myeloid leukemia (AML). To identify molecular targets on the surface of leukemia cells with EVI1high expression, we compared the gene expression profiles of several AML cell lines by DNA microarray
CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1 expression.
Cell line
View SamplesHuman subjects were randomized for treatment with a GnRH-analogue, Goserelin, which suppresses endogenous testosterone or placebo for 12 weeks. Strength training was performed during the last 8 weeks. The suppression of testosterone resulted in an attenuation of the normal muscle adaptation to strength training (increased muscle mass and strength). To identify molecular signals involved in the response to testosterone levels, biopsies were obtained 4 hours after the last training session and gene expression compared with Affymetrix 3' microarrays. This timepoint should capture goserelin effect on both constitutive expression, training induced changes as well as acute exercise induced (4 hours) differences in mRNA levels.
The activity of satellite cells and myonuclei following 8 weeks of strength training in young men with suppressed testosterone levels.
Sex, Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide approaches reveal functional vascular endothelial growth factor (VEGF)-inducible nuclear factor of activated T cells (NFAT) c1 binding to angiogenesis-related genes in the endothelium.
Specimen part, Treatment
View Samples