Xenium spatial transcriptomics identifies mesenchymal fibroblast expansion and conserved fibrotic ECM programs in keloid
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE341250 | GEO | 2026/07/24
REPOSITORIES: GEO
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Project description:Xenium spatial transcriptomics identifies mesenchymal fibroblast expansion and conserved fibrotic ECM programs in keloid
| PRJNA1500005 | ENA
Project description:This study investigated the effects of extracellular matrix (ECM) rigidty on gene expression patterns in normal dermal fibroblasts (NDFs) and keloid dermal fibroblasts (KDFs). Cells were cultured on collagen coated polyacrylamide hydrogels with elastic moduli mimicking normal skin (8 kPa) or keloid scar tissue (214 kPa), and changes in gene expression were profiled using next-generation RNA-sequencing. Differential gene expression analysis identified overall significant differences in gene expression between the NDF and KDF populations. Despite high levels of inter-patient heterogeneity in the KDF samples, further principal components analysis revealed a subset of genes (PC5) that were specifically regulated by ECM rigidity. Gene set enrichment analysis of the PC5 genes identified classic pathways associated with mechanotransduction, including Hippo Signalling and Regulation of the Actin Cytoskeleton, as well as genes associated with the Autophagy pathway. Additional in vitro studies and human tissue staining confirmed the biomechanical regulation of autophagic flux in NDFs and KDFs and differential remodelling of the lysosome in KDFs and keloid scars. Together, these findings implicate autophagy and lysosomal remodelling as biomechanically dysregulated pathways in keloid fibroblasts, and these mechanisms may contribute to scar pathogenesis.
2023-11-02 | GSE246562 | GEO
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:10X Genomics Xenium data from human Medulloblastoma samples. The data was acuired in the course of a study performing a comparison of four imaging-based ST methods – RNAscope HiPlex, Molecular Cartography, MERFISH/Merscope, and Xenium – together with sequencing-based ST (Visium). These technologies were used to study cryosections of medulloblastoma with extensive nodularity (MBEN), a tumor chosen for its distinct microanatomical features. Our analysis reveals that automated imaging-based ST methods are well suited to delineating the intricate MBEN microanatomy, capturing cell-type-specific transcriptome profiles. We devise approaches to compare the sensitivity and specificity of the different methods together with their unique attributes to guide method selection based on the research aim. Furthermore, we demonstrate how reimaging of slides after the ST analysis can markedly improve cell segmentation accuracy and integrate additional transcript and protein readouts to expand the analytical possibilities and depth of insights. This study highlights key distinctions between various ST technologies and provides a set of parameters for evaluating their performance. Our findings aid in the informed choice of ST methods and delineate approaches for enhancing the resolution and breadth of spatial transcriptomic analyses, thereby contributing to advancing ST applications in solid tumor research.
2025-03-17 | GSE291688 | GEO
Project description:Keloids are benign tumors of the dermis that form during a protracted wound healing process. Susceptibility to keloid formation occurs predominantly in people of African and Asian descent. The key alteration(s) responsible for keloid formation has not been identified and there is no satisfactory treatment for this disorder. The altered regulatory mechanism is limited to dermal wound healing, although several diseases characterized by an exaggerated response to injury are prevalent in individuals of African ancestry. We have observed a complex pattern of phenotypic differences in keloid fibroblasts grown in standard culture medium or induced by hydrocortisone. In this study Affymetrix-based microarray was performed on RNA obtained from fibroblasts cultured from normal scars and keloids grown in the absence and presence of hydrocortisone. We observed differential regulation of approximately 500 genes of the 38,000 represented on the Affymetrix chip. Of particular interest was increased expression of several IGF-binding and IGF-binding related proteins and decreased expression of a subset of Wnt pathway inhibitors and multiple IL-1-inducible genes. Increased expression of CTGF and IGFBP-3 was observed in keloid fibroblasts only in the presence of hydrocortisone. These findings support a role for multiple fibrosis-related pathways in the pathogenesis of keloids Keywords: cell-type comparison, drug treatment comparison Cell cultures were initiated from human biopsy material from normal dermal scars and keloids of adult males and females. Experimental cultures were derived from the first passage of cells thawed from liquid nitrogen. Cultures of fibroblasts from samples were grown with or without 1.5 micromolar hydrocortisone. RNA from each cell strain was isolated from three independent cell cultures and pooled, then run on an Affymetrix Human Genome U133 Plus 2.0 GeneChip.
2007-11-26 | E-GEOD-7890 | biostudies-arrayexpress
Project description:KRAS mutations are a predominant driver of metastatic colorectal cancer (mCRC), with approximately 10% of patients harboring the KRAS p.G12C variant. Despite the development of KRASG12C (G12Ci) and EGFR (EGFRi) inhibitors such as sotorasib and panitumumab, therapeutic resistance remains a major limitation. To define resistance mechanisms, we analyzed tissue biopsies from patients treated with G12Ci+EGFRi and employed Xenium spatial transcriptomics (Xenium ST), along with comprehensive multi-omics profiling of patient-derived xenograft (PDX) models. Known genomic alterations including NRAS p. Q61K mutations and KRASG12C amplifications were observed; however, non-genomic resistance was strongly associated with activation of the YAP-TEAD pathway. Xenium ST data revealed two key tumor subpopulations: tumor intestinal stem cells (TISCs), marked by upregulation of KRAS and YAP, and neuroendocrine-like (NE) cells, which showed KRAS upregulation alone. G12Ci+EGFRi-resistant PDX models were enriched for TISCs and associated stemness programs. The addition of a TEAD inhibitor (TEADi; IAG-933) to dual therapy induced deep tumor regression and suppressed KRAS, YAP, stemness pathways; however, NE-like cells were enriched following triple therapy. These findings suggest that TEADi enhances the efficacy of KRASG12C + EGFR inhibition by targeting TISCs but may not eliminate NE-like subpopulations, which could mediate TEAD-independent resistance and represent a therapeutic challenge.
2025-09-24 | GSE308699 | GEO
Project description:Keloids are benign tumors of the dermis that form during a protracted wound healing process. Susceptibility to keloid formation occurs predominantly in people of African and Asian descent. The key alteration(s) responsible for keloid formation has not been identified and there is no satisfactory treatment for this disorder. The altered regulatory mechanism is limited to dermal wound healing, although several diseases characterized by an exaggerated response to injury are prevalent in individuals of African ancestry. We have observed a complex pattern of phenotypic differences in keloid fibroblasts grown in standard culture medium or induced by hydrocortisone. In this study Affymetrix-based microarray was performed on RNA obtained from fibroblasts cultured from normal scars and keloids grown in the absence and presence of hydrocortisone. We observed differential regulation of approximately 500 genes of the 38,000 represented on the Affymetrix chip. Of particular interest was increased expression of several IGF-binding and IGF-binding related proteins and decreased expression of a subset of Wnt pathway inhibitors and multiple IL-1-inducible genes. Increased expression of CTGF and IGFBP-3 was observed in keloid fibroblasts only in the presence of hydrocortisone. These findings support a role for multiple fibrosis-related pathways in the pathogenesis of keloids Keywords: cell-type comparison, drug treatment comparison
2007-11-26 | GSE7890 | GEO
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:Keloid disease (KD) is a fibroproliferative cutaneous tumour characterised by heterogeneity, excess collagen deposition and aggressive local invasion. Normal and keloid scar tissues were analysed with a site-specific in situ approach through combined laser capture microdissection, as well as whole tissue biopsy and monolayer cell culture techniques.
2017-12-07 | E-MTAB-4945 | biostudies-arrayexpress