Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA361002 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The mouse anterior-posterior (A-P) axis polarization is preceded by formation of the distal visceral endoderm (DVE). However, the mechanism of the emergence of DVE cells is not well understood. Here, we show by in vitro culturing of embryos immediately after implantation in micro-fabricated cavities (narrow; 90 micro-meter, wide; 180 miro-meter in diameter) that the external mechanical cues exerted on the embryo, i.e. cultured in the narrow cavity, are crucial for DVE formation as well as elongated egg cylinder shape. This implies that these developmental events immediately after implantation are not simply embryo-autonomous processes but require extrinsic mechanical factors. Further whole genome-wide gene expression profiles with DNA microarray revealed that no significant difference of transcripts were evident with or without mechanical cues except DVE-related markers. Thus, we propose that external mechanical cues rather than not specific molecular pathways can trigger the establishment of the A-P axis polarization, which is one of the fundamental proccesses of mammalian embryogenesis. To identify the differences between the embryos cultured with or without external mechanical cues, we collected mouse embryos at E5.0 and cultured in the narrow (90 micro-meter in diameter) or the wide (180 micro-meter in diameter) cavities for 8 hours for RNA extraction and hybridization on Affymetrix microarrays. Arrays were performed using Affymetrix mouse Gene 1.0 ST arrays. Analysis was performed on three biological replicates of the mouse embryos cultured in the narrow and wide cavities for 8 hours.
2013-09-27 | E-GEOD-51198 | biostudies-arrayexpress
Project description:Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological ranges reset circadian clock phase and amplitude in cartilage and intervertebral disc tissues in vivo and in tissue explant cultures. Hyperosmolarity (but not hypo-osmolarity) resets clocks in young and ageing skeletal tissues and induce genome-wide expression of rhythmic genes in cells. Mechanistically, RNAseq and biochemical analysis revealed the PLD2-mTORC2-AKT-GSK3β axis as a convergent pathway for both in vivo loading and hyperosmolarity-induced clock changes. These results reveal diurnal patterns of mechanical loading and consequent daily surges in osmolarity as a bona fide tissue niche-specific time cue to maintain skeletal circadian rhythms in sync.
2023-08-17 | E-MTAB-12877 | biostudies-arrayexpress
Project description:p53 is a frequent target for mutation in human tumors and previous studies have revealed that these missense mutant proteins can actively contribute to tumorigenesis. To elucidate how mutant p53 might contribute to mammary carcinogenesis we employed a three-dimensional (3D) culture model. In 3D culture non-malignant breast epithelial cells form structures reminiscent of acinar structures found in vivo, whereas breast cancer cells form highly disorganized and in some cases invasive structures. We found that mutant p53 depletion is sufficient to phenotypically revert breast cancer cells to a more acinar-like morphology. Genome-wide expression analysis identified the sterol biosynthesis, or mevalonate, pathway as significantly upregulated by a tumor-derived mutant p53. Using statins and sterol biosynthesis intermediates, we demonstrate that this pathway is both necessary and sufficient for the phenotypic effects of mutant p53 on breast tissue architecture. Mutant p53 associates with the sterol gene promoters at least partly via the SREBP transcription factors. Finally, p53 mutation correlates with higher levels of sterol biosynthesis genes in human breast tumors. This activity of mutant p53 not only contributes insight into breast carcinogenesis, but also implicates the mevalonate pathway as a new therapeutic target for tumors bearing such mutations in p53.
2012-02-13 | GSE31812 | GEO
Project description:The mouse anterior-posterior (A-P) axis polarization is preceded by formation of the distal visceral endoderm (DVE). However, the mechanism of the emergence of DVE cells is not well understood. Here, we show by in vitro culturing of embryos immediately after implantation in micro-fabricated cavities (narrow; 90 micro-meter, wide; 180 miro-meter in diameter) that the external mechanical cues exerted on the embryo, i.e. cultured in the narrow cavity, are crucial for DVE formation as well as elongated egg cylinder shape. This implies that these developmental events immediately after implantation are not simply embryo-autonomous processes but require extrinsic mechanical factors. Further whole genome-wide gene expression profiles with DNA microarray revealed that no significant difference of transcripts were evident with or without mechanical cues except DVE-related markers. Thus, we propose that external mechanical cues rather than not specific molecular pathways can trigger the establishment of the A-P axis polarization, which is one of the fundamental proccesses of mammalian embryogenesis.
2013-09-27 | GSE51198 | GEO
Project description:Plakophilin 4 (PKP4) is a component of cell-cell junctions that regulates intercellular adhesion and Rho-signaling during cytokinesis with an unknown function during epidermal differentiation. Here we show that keratinocytes lacking PKP4 fail to develop a cortical actin ring, preventing adherens junction maturation and generation of tissue tension. Instead, PKP4-depleted cells display increased stress fibers. PKP4-dependent RhoA localization at AJs is required to activate a RhoA-ROCK2-MLCK-MLC2 axis and organize actin into a cortical ring. AJ-associated PKP4 provided a scaffold for the Rho activator ARHGEF2 and the RhoA effectors MLCK and MLC2, facilitating the spatio-temporal activation of RhoA signaling at cell junctions to allow cortical ring formation and actomyosin contraction. In contrast, association of PKP4 with the Rho suppressor ARHGAP23 reduced ARHGAP23 binding to RhoA which prevented RhoA activation in the cytoplasm and stress fiber formation. These data identify PKP4 as an AJ component that transduces mechanical signals into cytoskeletal organization.
2024-06-24 | GSE255172 | GEO
Project description:p53 is a frequent target for mutation in human tumors and previous studies have revealed that these missense mutant proteins can actively contribute to tumorigenesis. To elucidate how mutant p53 might contribute to mammary carcinogenesis we employed a three-dimensional (3D) culture model. In 3D culture non-malignant breast epithelial cells form structures reminiscent of acinar structures found in vivo, whereas breast cancer cells form highly disorganized and in some cases invasive structures. We found that mutant p53 depletion is sufficient to phenotypically revert breast cancer cells to a more acinar-like morphology. Genome-wide expression analysis identified the sterol biosynthesis, or mevalonate, pathway as significantly upregulated by a tumor-derived mutant p53. Using statins and sterol biosynthesis intermediates, we demonstrate that this pathway is both necessary and sufficient for the phenotypic effects of mutant p53 on breast tissue architecture. Mutant p53 associates with the sterol gene promoters at least partly via the SREBP transcription factors. Finally, p53 mutation correlates with higher levels of sterol biosynthesis genes in human breast tumors. This activity of mutant p53 not only contributes insight into breast carcinogenesis, but also implicates the mevalonate pathway as a new therapeutic target for tumors bearing such mutations in p53. RNA was isolated from three independent experiments of MDA-468.shp53 cells cultured under 3D conditions for 8 days in the presence or absence of DOX, reversed transcribed and hybridized to an Affymetrix GeneChip expression array. Data was processed using the Robust Multichip Average (RMA) algorithm to give expression signals and paired t-test was applied for each probe. Probes with 1% significance were selected for Ingenuity Pathway Analysis.
2012-02-13 | E-GEOD-31812 | biostudies-arrayexpress
Project description:Gain-of-function mutant p53 can function through a mutp53-MCM5-Sting-noncanonical NFkB signaling axis. We will analyze the transcriptional profiles of head and neck cancer stable cell lines UM-SCC-1 with overexpression of R273H mutant p53 and/or MCM5 under the normal culture condition.
2023-11-29 | GSE165374 | GEO
Project description:Mutant p53 Disrupts Mammary Acinar Morphogenesis via the Mevalonate Pathway
| PRJNA145251 | ENA
Project description:We have discovered that loss of wild-type p53 correlates with elevated expression of mevalonate pathway genes in murine liver cancer and in human tumors. Mechanistically p53 blocks activation of SREBP-2, the master transcriptional regulator of this pathway, by transcriptionally inducing the ABCA1 cholesterol transporter gene, which inhibits SREBP-2 maturation. In mice the increase in mevalonate gene expression occurs in premalignant p53-null hepatocytes at a stage when p53 is needed to actively suppress tumorigenesis. Either RNAi mediated suppression of key genes in the mevalonate pathway or pharmacological inhibition of its rate-limiting enzyme restricts the development of mouse hepatocellular carcinomas driven by p53 loss. Conversely, like p53 loss, ablation of ABCA1 promotes tumorigenesis in a murine model and is associated with increased SREBP-2 maturation. Our findings thereby demonstrate that repression of the mevalonate pathway is a crucial component of p53-mediated tumor suppression and outline the mechanism by which this occurs.
2018-10-23 | GSE121558 | GEO
Project description:exosomes isolated from: HT29+control shRNA; HT29+p53 shRNA; HCT116 WT p53; HCT116 mutant p53; HCT116 null p53; media used as negative control
2018-02-09 | MSV000082047 | MassIVE