Mechanisms of stretch-mediated skin expansion at single cell resolution [ATAC-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA523146 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8590752_1.fastq.gz | Fastqsanger.gz | |||
| SRR8590752_2.fastq.gz | Fastqsanger.gz | |||
| SRR8590753_1.fastq.gz | Fastqsanger.gz | |||
| SRR8590753_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Mechanisms of stretch-mediated skin expansion at single cell resolution [array]
| PRJNA521358 | 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 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: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 study design involves the proteomics characterization of primary skin fibroblast cell lines derived from skin biopsies from patients affected by either amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). Patients enrolled were divided in three groups: 1) ALS patients carrying the C9ORF72 repeat expansion as main genetic mutation (c9orf72 pos; n=6), 2) sporadic ALS patients, carrying mutations other than the C9ORF72 repeat expansion (c9orf72 neg; n=8), 3) FTD patients carrying the C9ORF72 repeat expansion (FTD; n=2). Total protein extracts were obtained from primary skin fibroblasts cultures and trypsin digested. Shotgun proteomics by LC-MS/MS (two technical replicates per sample) and systems biology analyses were performed as follows
2021-11-02 | PXD023866 | Pride
Project description:Skin systemic sclerosis (Scleroderma, SSc) is an autoimmune disease while its epigenetic regulatory mechanism is not known. We surveyed the genome-wide active regulatory elements in fresh human skin cells, using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq) in longitudinal skin from healthy volunteers and affected and unaffected skin from patients with SSc. We created robust pipelines that enable accurate single molecule counting and allelic discrimination from clinical material in vivo without clonal expansion. We generated high-resolution epigenetic regulomes of 9 cell types in normal and SSc skins, and identified 106044 cell type specific accessible sites. Motif analysis of these peaks predicted known and novel transcription factors regulating each cell type. For each cell type, we discovered thousands of accessible sites are differential in normal versus unaffected and affected skin from patients with SSc. We predicted novel transcription factors regulating SSc in a cell type specific manner, and predicted the relative contributions of each cell type in driving skin SSc. ATAC-seq also revealed novel elements that escape X chromosome inactivation, which coordinately impact genes with immune function.
2020-10-20 | GSE99702 | 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
Project description:Healthy skin is a tapestry of wild-type and mutant clones. Although injury can cooperate with Ras mutations to promote tumorigenesis, the consequences in genetically mosaic skin are unknown. Here, we show that wild-type cells suppress oncogenic Ras-induced aberrant growth after injury. While HrasG12V/+ and KrasG12D/+ cells outcompete wild-type cells in uninjured, mosaic tissue, their expansion is prevented after injury due to an increase in the fraction of proliferating wild-type cells. Mechanistically, we show that, unlike HrasG12V/+ cells, wild-type cells respond to autocrine and paracrine secretion of EGFR ligands, and this differential activation of the EGFR pathway explains the competitive switch during injury-repair. Inhibition of EGFR by both drug and genetic approaches diminished the proportion of dividing wild-type cells after injury, leading to the expansion of HrasG12V/+ cells. Increased wild-type cell proliferation through a global loss of the cell cycle inhibitor p21 counteracted the expansion of HrasG12V/+ cells even without injury. Thus, injury plays an unanticipated role in switching the competitive balance between oncogenic and wild-type cells in genetically mosaic skin.
2023-03-31 | GSE195892 | GEO
Project description:The development of meter-long axons within the nervous system is a remarkable, yet unresolved biological process. The most widely studied aspects of neuronal growth focus on the extension and chemotropism of growth cones. However, over the course of organismal development, short axons elongate up to one meter in length with the systemic expansion of mitotic tissues. The preeminent regulatory mechanism for such synchronized growth between the nervous system and the tissues it spans, is the biomechanical stretch of axons, a known stimulus of axon growth. Here, we reveal the transcriptional profile of stretch-mediated axon growth as found using embryonic rat dorsal root ganglia neurons stretch-grown in vitro.
2020-11-30 | GSE98535 | GEO
Project description:Mammalian skin wounds heal by forming fibrotic scars. We report that reindeer antler velvet exhibits regenerative wound healing, whereas identical injury to back skin forms scar. This regenerative capacity was retained following ectopic transplantation of velvet to scar-forming sites. Single-cell mRNA/ATAC-Sequencing revealed that while uninjured velvet fibroblasts resembled human fetal fibroblasts, back skin fibroblasts were enriched in pro-inflammatory features resembling adult human fibroblasts. Injury elicited site-specific immune polarization; back skin fibroblasts amplified the immune response, whereas velvet fibroblasts adopted an immunosuppressive state leading to restrained myeloid maturation and hastened immune resolution ultimately enabling myofibroblast reversion to a regeneration-competent state. Finally, regeneration was blunted following application of back skin associated immunostimulatory signals or inhibition of pro-regenerative factors secreted exclusive to velvet fibroblasts. This study highlights a unique model to interrogate mechanisms underlying divergent healing outcomes and nominates both decoupling of stromal-immune crosstalk and reinforcement of pro-regenerative fibroblast programs to mitigate scar.
2023-02-23 | PXD035749 | Pride