Mechanisms of stretch-mediated skin expansion at single cell resolution [array]
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PROVIDER: PRJNA521358 | ENA |
REPOSITORIES: ENA
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Project description:Mechanisms of stretch-mediated skin expansion at single cell resolution [ATAC-seq]
| PRJNA523146 | ENA
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
Project description:The ability of the skin to grow in response to stretching has been exploited in reconstructive surgery1. Although the response of epidermal cells to stretching has been studied in vitro2,3, it remains unclear how mechanical forces affect their behaviour in vivo. Here we develop a mouse model in which the consequences of stretching on skin epidermis can be studied at single-cell resolution. Using a multidisciplinary approach that combines clonal analysis with quantitative modelling and single-cell RNA sequencing, we show that stretching induces skin expansion by creating 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 step-by-step mechanisms that control stretch-mediated tissue expansion at single-cell resolution in vivo.
| S-EPMC7116042 | biostudies-literature
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.
2020-05-18 | GSE126734 | GEO
Project description:Interleukin 11 drives dermal fibroblast activation in mechanical stretch-mediated skin expansion
| PRJNA1121315 | ENA
Project description:In plastic and reconstructive surgery, mechanical stretch (MS) forces are frequently used to stimulate skin regeneration in order to produce additional skin for repairing tissue defects. Fibroblast activation in response to MS is crucial for skin growth during skin expansion. While its function in skin expansion is unknown, interleukin 11 (IL11) has been described as a cytokine that is increased in response to mechanical stimuli. In this study, we demonstrated that the expression of IL11 and IL11 receptor alpha subunit (IL11RA) was significantly increased in dermal fibroblasts (DFs) of the well-regenerated expanded skins (ESs) in human and mouse samples. However, IL11 was relatively lacking in the poorly-regenerated human ESs. Through the inhibition of IL11 signaling, MS-induced fibroblast proliferation, extracellular matrix (ECM) production, and myofibroblast activation were all inhibited in vitro. Consistently, depletion of IL11 signaling in vivo reduced skin regeneration during skin expansion, as evidenced by decreased dermal thickness and inhibited fibroblast function. Notably, transcriptomic analysis revealed that MS stimulation induced the upregulation of pathways associated with cell proliferation, collagen synthesis, stress response, and cell activation, whereas these pathways were downregulated in the IL11RA knockdown group. Mechanistically, we discovered that WNT5B acts as a downstream regulator of IL11-mediated cell activation in the presence of MS. Finally, the administration of recombinant IL11 via intradermal injection into mice significantly promoted fibroblast activation and halted the reduction in dermal thickness that occurred during skin expansion. In summary, our study demonstrated that IL11 signaling plays a crucial role in the activation of fibroblasts induced by MS, making it a promising target for clinical application in enhancing skin regeneration during skin expansion.
2025-08-03 | GSE269384 | GEO
Project description:Our understanding of how skin compartments coordinate in response to mechanical stretch induced regeneration is limited. After establishing a mouse scalp expansion model and defining the regenerative exhaustion phenotype, we collected corresponding expanded skin samples (Ctrl as DPE0, DPE8, DPE36) and performed single-cell RNA transcriptomic sequencing. We characterized the impaired proliferative and differentiation capacities, as well as compromised cellular adhesion in the basal stem cells of the interfollicular epidermis in the DPE36 samples. Additionally, we observed upregulation of Mmp2 and an imbalance in ECM degradation in the dermis of DPE36 samples. Our analysis provides a temporal transcriptomic atlas of the skin's mechanoresponsive mechanisms and sheds light on how a weakened dermal niche impacts stem cell stemness, ultimately leading to regenerative failure.
2025-08-17 | GSE281659 | GEO
Project description:Ultra high resolution breakpoint mapping using custom oligonucleotide arrays and array painting Keywords: Breakpoint mapping
2006-11-01 | GSE4297 | GEO
Project description:Context: Increased uterine stretch appears to increase the risk of preterm labour, but the mechanism is unknown. Objectives: To identify a targetable mechanism mediating the effect of stretch on human myometrium. Design: Myometrial explants, prepared from biopsies obtained at elective caesarean delivery, were either studied acutely, or were maintained in prolonged culture (up to 65 h) under tension with either a 0.6 g or 2.4 g mass, and compared using in vitro contractility, whole genome array, and qRT-PCR. Results: Increased stretch for 24 or 65 h increased potassium-induced and oxytocin-induced contractility. Gene array identified 62 differentially expressed transcripts after 65 h exposure to increased stretch. Two probes for gastrin-releasing peptide (GRP), a known stimulatory agonist of smooth muscle, were among the top five up-regulated by stretch (3.4-fold and 2.0-fold). Up-regulation of GRP by stretch was confirmed in a separate series of 10 samples using qRT-PCR (2.8-fold, P = 0.01). GRP stimulated contractions acutely when added to freshly obtained myometrial strips in 3 out of 9 cases, but Western blot demonstrated expression of the GRP receptor in 9 out of 9 cases. Prolonged incubation of stretched explants in the GRP antagonists PD-176252 or RC-3095 (65 and 24 h respectively) significantly reduced potassium chloride and oxytocin-induced contractility. Conclusion: Stretch of human myometrium increases contractility and stimulates the expression of a known smooth muscle stimulatory agonist, GRP. Incubation of myometrium in GRP receptor antagonists ameliorates the effect of stretch. GRP may be a target for novel therapies to reduce the risk of preterm birth in multiple pregnancy.
2012-06-15 | GSE31329 | GEO
Project description:Mechanical stress is a potent regulator of cell growth, contractility and gene regulation. Abnormal uterine distension during pregnancy increases the risk of preterm birth and likely activates crosstalk between multiple signaling networks with protein phosphorylation playing a critical role. Telomerized human uterine smooth muscle cells were exposed to 18% biaxial stretch for 5 min and the phosphoproteome was probed by mass spectrometry. We observed specific phospho-activation of mitogen activated protein kinase at threonine 183 and tyrosine 185, myosin regulatory light chain 9 at threonine 19, and heat shock protein 27 at serine 82. Our analysis revealed protein phosphorylation changes in signaling pathways related to actin cytoskeleton remodeling, activation of the focal adhesion kinase pathway, smooth muscle contraction and mechanistic target of rapamycin activation. These data point to potential mechanistic links between stretch-induced phosphorylation and development of the contractile phenotype in myometrial cells.
2019-04-10 | PXD002538 | Pride