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:Using an in vivo mouse model of stretch-mediated skin expansion, we have performed scRNAseq (10x Genomics) on control (CTRL) skin and expanded (EXP) skin at 3 time points: day 1, day 2 and day 4. Stretch-mediated expansion is used in reconstructive and cosmetic surgeries to produce extra skin, however the mechanisms behind it are not well understood. This study represents the first full skin scRNAseq study of in vivo stretch-mediated skin expansion.
2026-05-14 | GSE285079 | GEO
Project description: Not available
| S-EPMC7116042 | biostudies-literature
Project description:Using an in vivo mouse model of stretch-mediated skin expansion, we have performed bulk RNAseq on control (CTRL) skin fibroblasts and expanded (EXP) skin fibroblasts at 3 time points: day 1, day 2 and day 4. Stretch-mediated expansion is used in reconstructive and cosmetic surgeries to produce extra skin, however the mechanisms behind it are not well understood. Here we investigate the transcriptional changes occurring in fibroblasts upon expansion. We find downregulation of many extracellular matrix genes, including collagens, and upregulation of genes related to mitosis and sterol biosynthesis.
2026-05-14 | GSE284808 | GEO
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:Stretch-mediated tissue expansion is commonly used to grow extra skin for reconstructive surgeries. To ensure harmonious growth, the two main skin compartments, the epidermis and the dermis, must both expand in a coordinated manner. Although the epidermal response has been previously described, it remains unclear how fibroblasts, the main supporting cell type, respond to stretching in vivo. Here we map the transcriptional response of the entire skin during stretch-mediated tissue expansion, and we describe the fibroblast response to stretching in vivo. We show an increase in fibroblast volume accompanied by changes in organisation. We demonstrate that stretching forces fibroblasts to exit their quiescent state and restart proliferation. Concurrently, fibroblasts reduce collagen production and upregulate extracellular matrix remodelling factors, adopting a more embryonic-like program. Because embryonic fibroblasts are widely used as feeder layers to support the expansion of epidermal stem cells for clinical application, we leveraged this model to show that a low collagen state enhances epidermal stem cell self-renewal, thereby coordinating epidermal and dermal responses during skin expansion. These findings provide valuable insights to guide the design of in vivo stretch-mediated tissue expansion protocols and the production of in vitro skin grafts for clinical application.
2026-05-15 | GSE324558 | 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