Mechanical Strain Drives Myeloid Cell Differentiation Toward Pro-Inflammatory Subpopulations
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE175460 | GEO | 2021/05/25
REPOSITORIES: GEO
Similar Datasets
Project description:Mechanical Strain Drives Myeloid Cell Differentiation Toward Pro-Inflammatory Subpopulations
| PRJNA732424 | ENA
Project description:We quantify the effects of FAK inhibition on three-dimensional (3D) cultured human fibroblasts at the cellular and transcriptomic level using single cell RNA-sequencing. We demonstrate that mechanical stress induces pro-fibrotic fibroblast differentiation fates in large organisms, which can effectively be averted by FAK inhibition, which induces discrete fibroblast clusters that promote wound regeneration.
2021-02-24 | GSE167339 | GEO
Project description:Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such stress affects tumor cell behavior. Here we show that compressive stress stimulates migration of mammary carcinoma cells. The enhanced migration is accomplished by a subset of "leader cells" that extend filopodia at the leading edge of the cell sheet. Formation of these leader cells is dependent on cell microorganization and is enhanced by compressive stress. Accompanied by fibronectin deposition and stronger cell-matrix adhesion, the transition to leader-cell phenotype results in stabilization of persistent actomyosin-independent cell extensions and coordinated migration. Our results suggest that compressive stress accumulated during tumor growth can enable coordinated migration of cancer cells by stimulating formation of leader cells and enhancing cell-substrate adhesion. This novel mechanism represents a potential target for the prevention of cancer cell migration and invasion.
| S-EPMC3271885 | biostudies-other
Project description:Purpose: Intimal hyperplasia is the leading cause of graft failure in aortocoronary bypass grafts performed using human saphenous vein (SV). The long-term consequences of the altered pulsatile stress on the cells that populate the vein wall remain elusive, in particular onto saphenous vein progenitors (SVPs), adult cell phenotype of the human adventitia that upholds differentiation capacity. In the present study, we performed global transcriptomic profiling of SVPs that underwent in vitro uniaxial cyclic strain, a type of mechanical stimulation that we recently found to be involved in the pathology of the SV. Methods: To investigate the effect of mechanical strain on cultured cells, SVPs were subjected to cyclic strain using the FlexCell Tension Plus FX-5000T system. Cells were subjected to uniaxial cyclic deformation protocol (0-10% deformation, 1 Hz frequency), for 24 and 72 hours, while static controls were provided by seeding an equal amount of cells, under the same atmospheric conditions, but without mechanical stimulation. For RNA-Seq analysis, total RNA was extracted from 5 different donors of SVPs using TRIzol, treated with DNase I, and quantified by using NanoDrop-1000 spectrophotometer before integrity assessment with Agilent 2100 Bioanalyzer (RNA Integrity Number values >8). Results: Results showed a consistent stretch-dependent gene regulation in cyclically strained SVPs vs. controls, especially at 72hrs. We also observed a robust mechanically related overexpression of Adhesion Molecule with Ig Like Domain 2 (AMIGO2), a cell surface type I transmembrane protein involved in cell adhesion. The overexpression of AMIGO2 in stretched SVPs was associated with the activation of the transforming growth factor β pathway and modulation of cell signalling, cell-cell, and cell-matrix interactions. Conclusions: These results show that mechanical stress promotes SVPs' molecular phenotypic switching and increases their responsiveness to extracellular environment alterations, thus prompting the targeting of new molecular effectors to improve the outcome of bypass graft procedure.
2022-01-10 | GSE192712 | GEO
Project description:To study if non-invasive oral squamous cell carcinoma (OSCC) cells can acquire mechanical memory from stiff matrix and investigate the role of cell contractility in that process, Cal27 were conditioned (for 5 days) either by matrix stiffness or by direct modulation of cell contractility and then replated to a new niche lack of sources for the cells to learn. Cal27 with different types of conditioning were categorized either "Learn" or "Don't Lean/Forget" based on the existence of mechanical memory. Comparative gene expression profiling was done between "Learn" vs. "Don't Learn/Forget" Cal27 groups by RNA sequencing
2023-04-07 | GSE207685 | GEO
Project description:The mechanical effect of raised intraocular pressure is a recognised stimulus for optic neuropathy in primary open angle glaucoma (POAG). Characteristic extra-cellular matrix (ECM) remodelling accompanies axonal damage in the lamina cribrosa (LC) of the optic nerve head in POAG. Glial cells in the lamina cribrosa may play a role in this process but the precise cellular responses to mechanical forces in this region are unknown. The authors examined global gene expression profiles in lamina cribrosa cells exposed to cyclical mechanical stretch, with an emphasis on ECM genes. Experiment Overall Design: n=3 stretch and static control experiments. Experiment Overall Design: RNA pooled from each experiment and hybridised to individual experiment and control arrays.
2008-06-12 | E-GEOD-3166 | biostudies-arrayexpress
Project description:The mechanical effect of raised intraocular pressure is a recognised stimulus for optic neuropathy in primary open angle glaucoma (POAG). Characteristic extra-cellular matrix (ECM) remodelling accompanies axonal damage in the lamina cribrosa (LC) of the optic nerve head in POAG. Glial cells in the lamina cribrosa may play a role in this process but the precise cellular responses to mechanical forces in this region are unknown. The authors examined global gene expression profiles in lamina cribrosa cells exposed to cyclical mechanical stretch, with an emphasis on ECM genes. Keywords: microarray, ECM, glaucoma, mechanical stretch, lamina cribrosa
2005-08-21 | GSE3166 | GEO
Project description:To form new blood vessels (angiogenesis), endothelial cells (ECs) must be activated and acquire highly migratory and proliferative phenotypes. However, the molecular mechanisms that govern these processes are incompletely understood. Here, we show that Apelin signaling functions to drive ECs into such an angiogenic state. Zebrafish lacking Apelin signaling exhibit defects in endothelial tip cell morphology and sprouting. Using transplantation experiments, we find that in mosaic vessels, wild-type ECs leave the dorsal aorta (DA) and form new vessels while neighboring ECs defective in Apelin signaling remain in the DA. Mechanistically, Apelin signaling enhances glycolytic activity in ECs at least in part by increasing levels of the growth-promoting transcription factor c-Myc. Moreover, APELIN expression is regulated by Notch signaling in human ECs, and its function is required for the hypersprouting phenotype in Delta-like 4 (Dll4) knockdown zebrafish embryos. These data provide new insights into fundamental principles of blood vessel formation and Apelin signaling, enabling a better understanding of vascular growth in health and disease.
| S-EPMC7567607 | biostudies-literature
Project description:Skeletal integrity in humans and animals is maintained by daily mechanical loading. It has been widely accepted that osteocytes function as mechanosensors. Many biochemical signaling molecules are involved in the response of osteocytes to mechanical stimulation. The aim of this study was to identify genes involved in the translation of mechanical stimuli into bone formation. The four-point bending model was used to induce a single period of mechanical loading (comprising 300 cycles (2 Hz) using a peak magnitude of 60 N) on the right tibia, while the contra lateral left tibia served as control. Six hours after loading, the effects of mechanical loading on gene-expression were determined with microarray analysis. Protein expression of differentially regulated genes was evaluated with immunohistochemistry. Nine genes were found to exhibit a significant differential gene expression in LOAD compared to control. MEPE, Garnl1, V2R2B, and QFG TN1 olfactory receptor were up-regulated, and creatine kinase (muscle form), fibrinogen-B beta-polypeptide, monoamine oxidase A, troponin-C and kinesin light chain-C were down-regulated. Validation with real-time RT-PCR analysis confirmed the up regulation of MEPE and the down-regulation of creatine kinase (muscle form) and troponin-C in the loaded tibia. Immunohistochemistry showed that the increase of MEPE protein expression was already detectable six hours after mechanical loading. In conclusion, these genes probably play a role during translation of mechanical stimuli six hours after mechanical loading. The modulation of MEPE expression may indicate a connection between bone mineralization and bone formation after mechanical stimulation. Two groups: LOAD vs contralateral control and SHAM vs contralateral control (n=5/group)
2013-11-21 | E-GEOD-50707 | biostudies-arrayexpress
Project description:During the development, mechanical force plays an important role in shaping the inner ear and establishing regular cellular patterns, however, the effects of ubiquitous mechanical cues on cellular fate determination are not clear. Here we developed stiffness adjustable hydrogels for three-dimensional (3D) cochlear organoid culture, which could precisely simulate the mechanical force from the extracellular matrix (ECM) during the expansion of cochlear progenitor cells (CPCs) and organoid formation. Within a certain range, suitable stiffness can stimulate CPC proliferation through a mechanism requiring integrin/cytoskeleton/YAP signaling. Surprisingly, increasing stiffness could inhibit the proliferation of CPCs and induce the differentiation of organoids, which was mediated by the increased intracellular Ca2+ signaling in CPCs, and further activated Klf2 to promote the differentiation of HCs with bundles. Furthermore, this chemical-defined hydrogel is also suitable for 3D bioprinting, and we printed the spiral-like structure with CPCs and HCs, which provided a promising way for cochlear organoids to further improve our understanding of the organization of the inner ear and contribute to developing new therapeutic approaches for HCs regeneration.
2023-10-26 | GSE202640 | GEO