Somatic mutations activating MAPK signaling in disorders of brain overgrowth and in diffuse glioma have recently been reported in pediatric neurology. Here we developed a progressive zebrafish model of glioma based on somatic expression of oncogenes that activate MAPK-AKT signalling (H-RASG12V, K-RASG12D, AKT, EGFRv3, BRAFV600E) in neural progenitor cells. Oncogenic HRAS was the most effective in activating MAPK signaling and caused the development of different types of growth disorders in juvenile fish: from benign dysplasia/heterotopia to invasive tumors of the telencephalon, midbrain and cerebellum. We used this model to clarify the molecular events leading to malignant tumors instead of benign lesions. Specific signatures distinguish benign heterotopia from tumors and establish that tumors require persistent activation of MAPK/ERK. Moreover, analysis of global RNA expression showed that brain tumors expressed a gene signature similar to the mesenchymal glioblastoma subtype Overall design: We performed transcriptome analysis (RNA-Seq) of 3 UAS:HRASV12G brains, which carried tumorigenic lesions in the telencephalon, midbrain and IV ventricle and compared them with tumor free, age matched brains.
A novel brain tumour model in zebrafish reveals the role of YAP activation in MAPK- and PI3K-induced malignant growth.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Cell line
View SamplesWe aimed at analyzing the transcriptome changes associated with the deletion of a portion of the Alu element from MIR205HG transcript
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Cell line
View SamplesWe aimed at analyzing the transcriptome changes associated with MIR205HG knock-down in RWPE-1 cells
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
No sample metadata fields
View SamplesSome cancers evade targeted therapies through a mechanism known as lineage plasticity, whereby tumor cells acquire phenotypic characteristics of a cell lineage whose survival no longer depends on the drug target. Here we show, using in vitro and in vivo prostate cancer models, that these tumors can develop resistance to the antiandrogen drug enzalutamide by a phenotypic shift from androgen receptor (AR) dependent luminal epithelial cells to AR independent basal-like cells. This lineage plasticity is enabled by loss of TP53 and RB1 function, is mediated by increased expression of the reprogramming transcription factor SOX2 and can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression. Thus, mutations in tumor suppressor genes can create a state of increased cellular plasticity that, when challenged with antiandrogen therapy, promotes resistance through lineage switching. Overall design: LNCaP/AR prostate cell line was transduced with shNT or shTP53:RB1 hairpins and then RNA was harvested from these cell lines for gene epxression analysis.
SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer.
Cell line, Subject
View SamplesAntitoxins are becoming recognized as proteins that regulate more than their own synthesis; for example, we found previously that antitoxin MqsA represses the gene encoding the stationary phase sigma factor RpoS. Here, we investigated the physiological role of antitoxin DinJ of the DinJ/YafQ toxin/antitoxin system and found DinJ also affects the general stress response by decreasing RpoS levels. Corroborating the reduced RpoS levels upon producing DinJ, catalase activity, cell adhesins, and cyclic diguanylate decreased while swimming increased. Using a transcriptome search and DNA-binding assays, we determined that the mechanism by which DinJ reduces RpoS is by repressing cspE which encodes cold-shock protein CspE that inhibits translation of rpoS mRNA. Hence, DinJ influences the general stress response indirectly by regulating cspE.
Antitoxin DinJ influences the general stress response through transcript stabilizer CspE.
Time
View SamplesWe have used the citrus GeneChip array (GPL5731) to survey the transcription profiles of sweet orange in response to the bacterial pathogens Xanthomonas axonopodis pv. citri (Xac) and Xanthomonas axonopodis pv. aurantifolii (Xaa). Xac is the causal agent of the citrus canker disease on a wide range of citrus species, including sweet oranges (Citrus sinensis). On the other hand, Xaa is pathogenic to Mexican lime (Citrus aurantifolia) only, and in sweet orange it triggers a defense response. In order to identify the genes induced during the defense response (Xaa-responsive genes) or citrus canker development (Xac-responsive genes), we conducted microarrays hybridization experiments at 6 and 48 hours after bacterial infiltration (habi). The analysis revealed that genes commonly modulated by Xac and Xaa are associated with basal defenses normally triggered by pathogen-associated molecular patterns, including those involved in reactive oxygen species production and lignification. Significantly, Xac-infected leaves showed considerable changes in the transcriptional profiles of defense-, cell wall-, vesicle trafficking- and cell growth-related genes between 6 and 48 habi. This is consistent with the notion that Xac suppresses host defenses near the beginning of the infection and simultaneously changes the physiological status of the host to promote cell enlargement and division. Finally, Xaa triggered a MAP kinase signaling pathway involving WRKY and ethylene-responsive transcriptional factors known to activate downstream defense genes.
Transcriptional analysis of the sweet orange interaction with the citrus canker pathogens Xanthomonas axonopodis pv. citri and Xanthomonas axonopodis pv. aurantifolii.
No sample metadata fields
View SamplesPersister cells are a sub-population of all bacterial cultures which exhibit a non-inheritable, multi-drug tolerance when subjected to lethal antibiotic challenge. These persisters arise as a result of metabolic dormancy, and can resume growth subsequent to antibiotic challenge, leading to recalcitrance of bacterial infections.
Phosphodiesterase DosP increases persistence by reducing cAMP which reduces the signal indole.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Cell line, Treatment, Time
View SamplesExposure to high irradiance results in dramatic changes in nuclear gene expression in plants. However, little is known about the mechanisms by which changes in irradiance are sensed and how the information is transduced to the nucleus to initiate the genetic response. To investigate whether the photoreceptors are involved in the response to high irradiance, we analyzed expression of ELIP1, ELIP2, APX2 and LHCB2.4 in the phyA, phyB, cry1 and cry2 photoreceptor mutants and hy5 and hyh transcription factor mutants. Following exposure to high intensity white light for 3 h (HL, 1000 micro mol quanta m-2 s-1) expression of ELIP1/2 and APX2 was strongly induced and LHCB2.4 expression repressed in wild type. The cry1 and hy5 mutants showed specific mis-regulation of ELIP1/2 and we show that the induction of ELIP1/2 expression is mediated via CRY1 in a blue light intensity-dependent manner. Furthermore, using the Affymetrix Arabidopsis 24K Gene-Chip we showed that 77 of the HL responsive genes are regulated via CRY1, and 26 of those genes were also HY5 dependent. As a consequence of the mis-regulation of these genes the cry1 mutant displayed a high irradiance-sensitive phenotype with significant photoinactivation of PSII, indicated by reduced Fv/Fm. Thus, we describe a novel function of CRY1 in mediating plant responses to high irradiances that is essential to the induction of photoprotective mechanisms. This indicates that high irradiance can be sensed in a chloroplast-independent manner by a cytosolic/nucleic component.
Genome-wide gene expression analysis reveals a critical role for CRYPTOCHROME1 in the response of Arabidopsis to high irradiance.
No sample metadata fields
View Samples