Single-cell and spatial transcriptomic atlas of pathological scars uncovers neuro-fibroblast crosstalk mechanisms across scar types
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PROVIDER: PRJNA1321889 | ENA |
REPOSITORIES: ENA
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Project description:Pathological scars, including hypertrophic scars and keloids, arise from excessive production and deposition of connective tissue such as collagen during wound healing, posing significant clinical challenges. Understanding the cellular and molecular dynamics underlying these scars is critical for developing effective therapies. Here, we integrate single-cell and spatial transcriptomics to characterize the cellular heterogeneity and molecular signatures of key scar-associated cell types, including pericytes, fibroblasts, and endothelial cells. Notably, we identify ECM-activated fibroblasts as a prominent subtype associated with pathological scarring. Cell-cell communication analysis reveals significantly enhanced interactions between fibroblasts and neural cells in pathological scars, especially in hypertrophic scars—a finding that aligns with clinical features such as fibrosis and pruritus. Moreover, we identify subtype-specific ligand-receptor pairs, including LAMB2–ITGA6 in hypertrophic scar and NLGN2–NRXN1 in keloid, mediating these fibroblast–neural communications. To support future research, we developed CellCellMarker 3.0, an updated and curated database integrating experimentally validated and transcriptomics-derived scar marker genes, along with ScarGPT, an intelligent Q&A system optimized using the DeepSeek R1 large language model, integrated with CellCellMarker data and a large corpus of scar-related publications.
2025-09-14 | GSE307504 | GEO
Project description:Fibrosis is vaguely described as connective tissue deposition that can be excessive in pathological conditions. This suggests a quantitative spectrum of fibrosis wherein there can be more or less extracellular matrix (ECM), which in the context of a repairing skin wound could reflect the range from normal scar to keloid. This depiction, however, does not encompass the potential qualitative differences between normal and pathological scars. In keloids, the markedly different physical (hard and dense) and histological (hyalinization) characteristics compared to normal scars indicate an altered and inappropriate matrix, rather than simply too much. With this quantitative discovery-based proteomics we provide a thorough molecular description of keloid lesions relative to normal scars, which is an essential step towards our understanding of this problem.
2019-12-03 | PXD015057 | Pride
Project description:We hypothesize that, the mTOR pathway is a dominant pathway in cultured keloid and hypertrophy scar fibriblasts compared to normal skin cells. Certain pathway changes can be detected after medication treatment. Global gene expression in RNA samples from rapamycin and tacrolimus treated fibroblasts (from normal skin and hypertrophic scars, keloid scars) is assayed to study the possibility to use mTOR inhibitors as potential drug to treat abnormal scarring. We investigated the difference between normal wound healing and hypertrophic scars and keloids as well.
2014-05-20 | E-MTAB-2509 | biostudies-arrayexpress
Project description:Keloids are scars that extend beyond original wounds and are resistant to treatment. In order to improve understanding of the molecular basis of keloid scarring, we have assessed the genomic profiles of keloid fibroblasts and keratinocytes. Skin and scar tissues were obtained for isolation of primary keratinocytes and fibroblasts. Keloid scars were excised from patients undergoing scar excision surgery, normal skin samples were isolated from patients undergoing elective plastic surgery. Primary culters were prepared for keratinocytes and fibroblasts, and were harvested for analysis up to passage three. Nine keloid scars, for adjacent non-lesional keloid skin samples, and three normal skin samples were obtained and cultured. RNA was isolated using RNeasy, and quality verified using an Agilent 2100 Bioanalyzer. Labeling and hybridization to Affymetrix Human Gene 1.0 ST microarray chips was performed by the Vanderbilt Genome Sciences Resource at Vanderbilt University Medical Center.
2013-05-28 | E-GEOD-44270 | biostudies-arrayexpress
Project description:Keloid scars is a pathologic fibro-proliferative disorders of the skin, which exhibit abnormal phenotypes including fibroblasts proliferation and collagen deposits. There have been several treatments of keloids including conventional surgical therapies and adjuvant therapies, but a high recurrence rate of keloids was also observed after treatment. Quantitative proteomics approach has been proved an efficient approach to investigate pathological mechanism and novel biomarkers. In this study, we present a label-free quantitative proteomics analysis to explore differential protein expression profiles in normal skin and keloid scar tissues based on nano-liquid chromatography and tandem mass spectrometry (Nano-LC–MS/MS). The study results displayed a more comprehensive keloid protein expression landscape and provided novel pathological insight of keloid.
2023-03-11 | PXD029631 | Pride
Project description:Background Hypertrophic scars and keloids are both pathological scars with similar appearance and pathological features. Currently, the differential diagnosis of the two mainly depends on the subjective judgment of physicians, and there is a lack of objective diagnostic indicators and treatment methods. Objectives To provide single-cell level evidence and new approaches for the differential diagnosis and clinical treatment of hypertrophic scars and keloids. Methods Single-cell RNA sequencing (scRNA-seq) was performed on a hypertrophic scar and a keloid tissue from the same patient to compare the differences in the cellular and tissue microenvironments of the two conditions. Results ScRNA-seq results depicted the distribution of cell subpopulations and different microenvironments between hypertrophic scars and keloids. Conclusions The results of the analysis showed significant differences in cell subcluster distribution and cell communication between hypertrophic scars and keloids. This study demonstrated the potential of scRNA-seq to differentiate the two conditions and provide a new approach to refine differential diagnosis and a possible target for therapeutic research.
2024-11-15 | GSE243716 | GEO
Project description:The mammalian heart possesses a poor ability to regenerate after acute ischemic cardiac injury and lost cardiac muscle is replaced by scar tissue. Multiple clinical studies demonstrate that the size of scar tissue following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors that regulate the size of scar after ischemic cardiac injury. In this report, we demonstrate that collagen V, a fibrillar collagen and a minor constituent of heart scars regulates the size of heart scars after ischemic cardiac injury. Depletion of collagen V in heart scars in two independent animal models led to a significant and paradoxical increase in post infarction scar tissue size with worsening of heart function. A systems genetics approach analyzing genes versus traits across 100 in-bred strains of mice independently demonstrated that collagen V is a critical driver of post injury heart function. We show that collagen V deficiency alters the ultra-structure and mechanical properties of scar tissue that make it more vulnerable to expansion. There is altered reciprocal feedback between matrix and cells that induce expression of specific mechanosensitive integrins which drive fibroblast activation and increased ECM gene expression. Scar size increases. Administration of cilengitide, an inhibitor of specific integrins, completely rescues the phenotype of increased post injury scarring, myofibroblast formation and cardiac dysfunction in collagen V deficient mice. These observations demonstrate that collagen V, a structural constituent of heart scar tissue regulates scar size in an integrin dependent manner.
2020-06-05 | GSE151834 | GEO
Project description:The mammalian heart possesses a poor ability to regenerate after acute ischemic cardiac injury and lost cardiac muscle is replaced by scar tissue. Multiple clinical studies demonstrate that the size of scar tissue following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors that regulate the size of scar after ischemic cardiac injury. In this report, we demonstrate that collagen V, a fibrillar collagen and a minor constituent of heart scars regulates the size of heart scars after ischemic cardiac injury. Depletion of collagen V in heart scars in two independent animal models led to a significant and paradoxical increase in post infarction scar tissue size with worsening of heart function. A systems genetics approach analyzing genes versus traits across 100 in-bred strains of mice independently demonstrated that collagen V is a critical driver of post injury heart function. We show that collagen V deficiency alters the ultra-structure and mechanical properties of scar tissue that make it more vulnerable to expansion. There is altered reciprocal feedback between matrix and cells that induce expression of specific mechanosensitive integrins which drive fibroblast activation and increased ECM gene expression. Scar size increases. Administration of cilengitide, an inhibitor of specific integrins, completely rescues the phenotype of increased post injury scarring, myofibroblast formation and cardiac dysfunction in collagen V deficient mice. These observations demonstrate that collagen V, a structural constituent of heart scar tissue regulates scar size in an integrin dependent manner.
2020-06-04 | GSE151695 | GEO
Project description:The goal was to obtain expression data from the deep cones in early human hypertrophic scars to be used to confirm expression data obtained in a porcine model. Three samples of early human hypertrophic scar were obtained and processed with the Affymetrix Human GeneChip® Human Genome U133 plus 2.0. Sample demographics were Black 2, White 1; upper extremity 2, neck 1; times since injury 6.7 months and 10.8 months; and patient ages were 19 and 54.
2011-12-31 | E-GEOD-26213 | biostudies-arrayexpress
Project description:It is well accepted that elevated mechanical tension of the skin surrounding a healing wound stimulates a fibrotic cascade of events and contributes to an increased size of scars. A laxity paradox in the field of hair transplantation describes a phenomenon opposing this view. During Strip Follicular Unit Transplantation (Strip FUT), surgeons remove a strip of scalp skin (approximately 5 cm x 10 cm, depending on the number of hair follicles required) from the occipital scalp, which is then used to harvest hair follicles that will be transplanted into the balding frontal scalp. Most patients with normal scalp skin laxity heal with narrow normotrophic scars, while a small number of patients (14%) with very loose scalp skin, and so low residual skin tension, heal with post operating scar widening (4 - 12 mm). These scars, referred to as stretched scars in the hair transplantation field, often require revision surgery or secondary hair grafting into the scar. We hypothesise that stretched scars present a unique transcriptional signature different from other types of scars. To determine the gene expression profile of stretched scars, we used Affymetrix microarrays to perform profiling of fibrotic dermis and the surrounding patient-matched healthy dermis.
2022-12-31 | GSE162904 | GEO