Similar Datasets
Project description:Metastatic cancer cells traverse tight junctions that exert forces on their nucleus and the genomic contents within. Cancerous tumors are highly heterogeneous and not all cells within them can achieve such a feat. Here, we investigated what initial genome architecture characteristics favor the constricted migratory ability of cancer cells and which arise only after passage through multiple constrictions. We identified a cell surface protein (ITGB4) whose expression correlates with increased initial constricted migration ability in human melanoma A375 cells. Sorting out this subpopulation allowed us to identify cellular and nuclear features that pre-exist and favor migration, as well as alterations that only appear after cells have passed through constrictions. We identified specific genomic regions that experienced altered genome spatial compartment profiles only after constricted migration. Our study reveals 3D genome structure contributions to both selection and induction mechanisms of cell fate change during cancer metastasis.
2024-08-26 | GSE275396 | GEO
Project description:Metastatic cancer cells traverse tight junctions that exert forces on their nucleus and the genomic contents within. Cancerous tumors are highly heterogeneous and not all cells within them can achieve such a feat. Here, we investigated what initial genome architecture characteristics favor the constricted migratory ability of cancer cells and which arise only after passage through multiple constrictions. We identified a cell surface protein (ITGB4) whose expression correlates with increased initial constricted migration ability in human melanoma A375 cells. Sorting out this subpopulation allowed us to identify cellular and nuclear features that pre-exist and favor migration, as well as alterations that only appear after cells have passed through constrictions. We identified specific genomic regions that experienced altered genome spatial compartment profiles only after constricted migration. Our study reveals 3D genome structure contributions to both selection and induction mechanisms of cell fate change during cancer metastasis.
2024-08-26 | GSE275395 | GEO
Project description:Deciphering Pre-existing and Induced 3D Genome Architecture Changes involved in Constricted Melanoma Migration
| PRJNA1150595 | ENA
Project description:Deciphering Pre-existing and Induced 3D Genome Architecture Changes involved in Constricted Melanoma Migration (RNA-Seq)
| PRJNA1150602 | ENA
Project description:Deciphering Pre-existing and Induced 3D Genome Architecture Changes involved in Constricted Melanoma Migration (Hi-C)
| PRJNA1150603 | ENA
Project description:Alginate hydrogels have been used as a biomaterial for 3D culturing for several years. Here, gene expression patterns in melanoma cells cultivated in 3D alginate are compared to 2D cultures. It is well-known that 2D cell culture is not resembling the complex in vivo situation well. However, the use of very intricate 3D models does not allow performing high-throughput screening and analysis is highly complex. 3D cell culture strategies in hydrogels will better mimic the in vivo situation while they maintain feasibility for large-scale analysis. As alginate is an easy-to-use material and due to its favorable properties, it is commonly applied as a bioink component in the growing field of cell encapsulation and biofabrication. Yet, only a little information about the transcriptome in 3D cultures in hydrogels like alginate is available. In this study, changes in the transcriptome based on RNA-Seq data by cultivating melanoma cells in 3D alginate are analyzed and reveal marked changes compared to cells cultured on usual 2D tissue culture plastic. Deregulated genes represent valuable cues to signaling pathways and molecules affected by the culture method. Using this as a model system for tumor cell plasticity and heterogeneity, EGR1 is determined to play an important role in melanoma progression.
| S-EPMC8394053 | biostudies-literature
Project description:Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly understood within the local chromatin environment surrounding replication origins. To reveal how the chromatin architecture modulates origin selection and activation, we "footprinted" nucleosomes, transcription factors, and replication proteins at multiple points during the Saccharomyces cerevisiae cell cycle. Our nucleotide-resolution protein occupancy profiles resolved a precise ORC-dependent footprint at 269 origins in G2. A separate class of inefficient origins exhibited protein occupancy only in G1, suggesting that stable ORC chromatin association in G2 is a determinant of origin efficiency. G1 nucleosome remodeling concomitant with pre-RC assembly expanded the origin nucleosome-free region and enhanced activation efficiency. Finally, the local chromatin environment restricts the loading of the Mcm2-7 double hexamer either upstream of or downstream from the ARS consensus sequence (ACS).
| S-EPMC4298139 | biostudies-literature
Project description:A long-standing objective in materials research is to effectively heal fabrication defects or to remove pre-existing or environmentally induced damage in materials. Silicon carbide (SiC) is a fascinating wide-band gap semiconductor for high-temperature, high-power and high-frequency applications. Its high corrosion and radiation resistance makes it a key refractory/structural material with great potential for extremely harsh radiation environments. Here we show that the energy transferred to the electron system of SiC by energetic ions via inelastic ionization can effectively anneal pre-existing defects and restore the structural order. The threshold determined for this recovery process reveals that it can be activated by 750 and 850 keV Si and C self-ions, respectively. The results conveyed here can contribute to SiC-based device fabrication by providing a room-temperature approach to repair atomic lattice structures, and to SiC performance prediction as either a functional material for device applications or a structural material for high-radiation environments.
| S-EPMC4557342 | biostudies-literature
Project description:The microvasculature continuously adapts in response to pathophysiological conditions to meet tissue demands. Quantitative assessment of the dynamic changes in the coronary microvasculature is therefore crucial in enhancing our knowledge regarding the impact of cardiovascular diseases in tissue perfusion and in developing efficient angiotherapies. Using confocal microscopy and thick tissue sections, we developed a 3D fully automated pipeline that allows to precisely reconstruct the microvasculature and to extract parameters that quantify all its major features, its relation to smooth muscle actin positive cells and capillary diffusion regions. The novel pipeline was applied in the analysis of the coronary microvasculature from healthy tissue and tissue at various stages after myocardial infarction (MI) in the pig model, whose coronary vasculature closely resembles that of human tissue. We unravelled alterations in the microvasculature, particularly structural changes and angioadaptation in the aftermath of MI. In addition, we evaluated the extracted knowledge's potential for the prediction of pathophysiological conditions in tissue, using different classification schemes. The high accuracy achieved in this respect, demonstrates the ability of our approach not only to quantify and identify pathology-related changes of microvascular beds, but also to predict complex and dynamic microvascular patterns.
| S-EPMC5789835 | biostudies-literature
Project description:The advanced development of synthetic lethality has opened the doors for specific anti-cancer medications of personalized medicine and efficient therapies against cancers. One of the most popular approaches being investigated is targeting DNA repair pathways as the implementation of the PARP inhibitor (PARPi) into individual or combinational therapeutic schemes. Such treatment has been effectively employed against homologous recombination-defective solid tumors as well as hematopoietic malignancies. However, the resistance to PARPi has been observed in both preclinical research and clinical treatment. Therefore, elucidating the mechanisms responsible for the resistance to PARPi is pivotal for the further success of this intervention. Apart from mechanisms of acquired resistance, the bone marrow microenvironment provides a pre-existing mechanism to induce the inefficiency of PARPi in leukemic cells. Here, we describe the pre-existing and acquired mechanisms of the resistance to PARPi-induced synthetic lethality. We also discuss the potential rationales for developing effective therapies to prevent/repress the PARPi resistance in cancer cells.
| S-EPMC9741207 | biostudies-literature