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Mechanisms of stretch-mediated skin expansion at single cell resolution [ATAC-seq]

ABSTRACT: The ability of the skin to expand in response to stretching has, for decades, been exploited in reconstructive surgery. Several studies have investigated the response of stretching epidermal cells in vitro. However, it remains unclear how mechanical forces affect epidermal stem cell behaviour in vivo. Here, we develop a mouse model in which the temporal consequences of the stretching the skin epidermis can be studied. Using a multidisciplinary approach that combines clonal analysis and mathematical modelling, we show that mechanical force induces skin expansion by promoting the renewal of epidermal stem cells. This occurs through a structured response in which cell fates are coordinated locally by stem cells that switch between states primed for renewal or differentiation. Transcriptional and chromatin profiling identifies the gene regulatory networks modulated by mechanical force. Using a combination of pharmacological inhibition and several conditional gene loss-of-function mouse mutants, we dissect the signalling pathways that control force-mediated tissue expansion.

ORGANISM(S): Mus musculus

PROVIDER: GSE126734 | GEO | 2020/05/18

REPOSITORIES: GEO

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Mechanisms of stretch-mediated skin expansion at single cell resolution [array]

Project description:The ability of the skin to expand in response to stretching has, for decades, been exploited in reconstructive surgery. Several studies have investigated the response of stretching epidermal cells in vitro. However, it remains unclear how mechanical forces affect epidermal stem cell behaviour in vivo. Here, we develop a mouse model in which the temporal consequences of the stretching the skin epidermis can be studied. Using a multidisciplinary approach that combines clonal analysis and mathematical modelling, we show that mechanical force induces skin expansion by promoting the renewal of epidermal stem cells. This occurs through a structured response in which cell fates are coordinated locally by stem cells that switch between states primed for renewal or differentiation. Transcriptional and chromatin profiling identifies the gene regulatory networks modulated by mechanical force. Using a combination of pharmacological inhibition and several conditional gene loss-of-function mouse mutants, we dissect the signalling pathways that control force-mediated tissue expansion. We used microarray to molecularly profile basal cells isolated from the interfolliular epidermis during force-mediated tissue expansion and after 12-O-Tetradecanoylphorbol-13-acetate (TPA) tretment.

2020-05-18 | GSE126231 | GEO

Single Cell RNA-sequencing of murine back skin interfollicular epidermis basal cells

Project description:The ability of the skin to grow in response to stretching has, for decades, been exploited in reconstructive surgery. The response of epidermal cells to stretching has been studied in vitro. However, it remains unclear how mechanical forces affect epidermal cell behaviour in vivo. Here, we develop a mouse model in which the consequences of stretching on skin epidermis can be studied. Using a multidisciplinary approach that combines clonal analysis with quantitative modelling and single-cell RNA-seq, we show that stretching induces skin expansion by a transient bias in the renewal activity of epidermal stem cells, while a second subpopulation of basal progenitors remains committed to differentiation. Transcriptional and chromatin profiling identifies how cell states and gene regulatory networks are modulated by stretching. Using pharmacological inhibitors and mouse mutants, we define the mechanisms that control stretch-mediated tissue expansion.

2020-05-18 | GSE146637 | GEO

Stem cell dynamic and signalling controlling mechanical force mediated skin expansion

Project description:Stem cell dynamic and signalling controlling mechanical force mediated skin expansion

| PRJNA523144 | ENA

Microarray data of rat expanded skin tissue

Project description:The skin expansion technique is widely applied in Plastic and Reconstructive Surgeries. Skin expansion induces skin growth and is an ideal approach for large-scale skin deformity reconstruction. However, the capacity for skin expansion is limited and searching for ways to enhance the expansion efficiency is a challenge. In this experiment, we aimed to explore the possible mechanism of skin expansion, and to find a potential therapeutic target on promoting skin growth.

2020-03-04 | E-MTAB-8304 | biostudies-arrayexpress

Mechanical stretch promotes invasion of lung cancer cells via activation of tumor necrosis factor-alpha

Project description:Most of the gas exchange in the human body is carried out by the lungs, and the physiological activities of the lungs are uninterrupted. Due to the deterioration of the external environment, pulmonary cell lesions are common clinical lung diseases. Mechanical cyclic stretching is one kind of bionic technology to observe lung cancer cells. The A549 cell line is the human lung adenocarcinoma cell line derived from a primary lung tumor. This study investigated the effects of mechanical cyclic stretching on A549 cell activity and gene expression profile. Whereas mechanical cyclic stretching had no significant difference in colony formation and cell migration of A549 cells, the cell invasion increased significantly in A549 cells after stretching. In addition, the microarray data showed that mechanical cyclic stretching altered gene expression, induced inflammation of cells, and activation of Wnt/β-catenin and tumor necrosis factor pathways. More importantly, mechanical cyclic stretching activated the expression of tumor necrosis factor-alpha (TNF-α) protein. Therefore, the increase of cell invasion induced by mechanical cyclic stretching might be associated with the activation of TNF-α in human lung adenocarcinoma cells.

2023-04-07 | GSE214041 | GEO

Both wnt signaling and epidermal stem cell-derived exosomes are involved in epidermal development

Project description:Millions suffer from skin diseases. Functional epidermal stem cells are needed in skin therapy or drug screening in vitro. We obtained functional epidermal stem cells with intact stemness and cell junctions by treating them with wnt3a. Moreover, epidermal stem cell-derived exosomes were useful in epidermal development. Finally, functional epidermal 3D organoids with polarity were cultured using wnt3a and the supernatant derived from epidermal stem cells and fresh medium in a 1:1 ratio. These results provide novel directions for the improvement of skin organoids and their potential in clinical application.

2020-07-14 | PXD020351 | iProX

Long-term expansion and differentiation of adult murine epidermal stem cells in three-dimensional organoid cultures

Project description:Mammalian epidermal stem cells maintain homeostasis of skin epidermis and contribute to its regeneration throughout adult life. While two-dimensional mouse epidermal stem cell cultures have been established decades ago, a long-term, feeder cell- and serum-free culture system recapitulating murine epidermal architecture has not been available. Here we describe an epidermal organoid culture system that allows long-term, genetically stable expansion of adult epidermal stem cells. Our epidermal expansion media combines atypically high calcium concentrations, activation of cyclic AMP, FGF and R-spondin signaling with inhibition of BMP signaling. Organoids are established robustly from adult mouse skin and expand over at least 6 months, while maintaining the basal-apical organization of the mouse interfollicular epidermis. The system represents a powerful tool to study epidermal homeostasis and disease in vitro.

2019-04-01 | GSE104521 | GEO

Mechanical Tension Mobilizes Lgr6+ Epidermal Stem Cells to Drive Skin Growth

Project description:Mechanical Tension Mobilizes Lgr6+ Epidermal Stem Cells to Drive Skin Growth

| PRJNA775997 | ENA

Phosphoproteome of cyclic stretch A549 and IMR-90

Project description:Lung cancer is one of the leading causes of death. However, most of the researches were based on the traditional cell-culturing method. Whereas cells of lung are subjected to the mechanical forces periodically while breathing. In the present study, we applied cyclic stretch to stimulate the continuously contracting physical condition. We uncovered the stretching force-induced phosphoproteome in lung cancer cell A549 and fibroblast IMR-90. 2048 and 2604 phosphosites corresponding to 837 and 1008 phosphoproteins were identified in A549 and IMR-90, respectively. Interestingly, cytoskeleton reorganization and mitochondrial localization were enriched in the significantly expressed phosphoproteins in response to cyclic stretch. Indeed, we found this physical stress changed cell alignment thus disrupted mitochondrial dynamics. We proved that mitochondrial fusion is induced by uniaxial stretch in 2 cell lines. This study reveals the molecular mechanism of cyclic stretch and supports that stretching force enhanced cellular rearrangement and mitochondrial fusion in lung cells.

2021-09-08 | PXD012010 | Pride

Gene expression changes under cyclic mechanical stretch in rat retinal Muller cells

Project description:The retina is often subjected to tractional forces in a variety of conditions, for instance, pathological myopia, proliferative vitreoretinopathy. As the predominant glial element in the sensory retina, Muller cells are responsible for the homeostatic and metabolic support of retinal neurons and active players in virtually all forms of retinal injury and disease. Besides, Muller cells span the entire retinal thickness, extending from the inner to the outer limiting membranes, with cell bodies located in the inner nuclear layer and lateral processes expanding into the plexiform layers of the tissue. Because of this unique morphology, Muller cells can sense even minute changes in the retinal structure because of the mechanical stretching of their long processes or side branches. Thus, itM-bM-^@M-^Ys reasonable to infer that Muller cells also participate in ocular diseases when the retina is overstretched. In this study, we aim to investigate the whole genome regulation of Muller cells under mechanical stretching, which may help in excluding possible molecular mechanisms that would account for many retinal diseases in which the retina is often subjected to mechanical forces. We used microarrays to identify patterns of gene expression changes induced by cyclic mechanical stretching in Muller cells. Rat Muller cells were seeded onto flexible bottom culture plates and subjected to a cyclic stretching regimen of 15% equibiaxial stretching for 1 and 24 h.Muller cells cultured under the same conditions but with no applied mechanical strain were considered as the unstretched control. At each time points (1 and 24 h), three totally independent experiments (3 stretched samples and 3 control samples) were conducted. Muller cells were selected for RNA extraction and hybridization on Affymetrix microarrays. Stretch (S); Control (C)

2013-01-16 | E-GEOD-43516 | biostudies-arrayexpress

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