Exploring an essential biomarker in pulmonary fibrosis: an integrated and cross-disease approach with spatial transcriptomics and single-cell RNA sequencing (Spatial Transcriptomics)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE263976 | GEO | 2025/06/02
REPOSITORIES: GEO
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Project description:We cross-sectionally examined various interstitial lung diseases (ILDs) via spatial transcriptomics of human samples. We unveiled crucial gene expression patterns and molecules involving fibrosis, exploring prognostic significance of this molecule in unclassifiable ILDs.
2025-06-02 | GSE295619 | GEO
Project description:Fibrosing interstitial lung diseases (ILDs) encompass a diverse range of scarring disorders that lead to progressive lung failure. Previous gene expression profiling studies focused on idiopathic pulmonary fibrosis (IPF) and bulk tissue samples. We employed digital spatial profiling to gain new insights into the spatial resolution of gene expression across distinct lung microenvironments (LMEs) in IPF, chronic hypersensitivity pneumonitis (CHP) and non-specific interstitial pneumonia (NSIP). We identified differentially expressed genes between LMEs within each condition, and across histologically similar regions between conditions. Uninvolved areas in IPF and CHP were remarkably distinct from normal controls, and displayed potential therapeutic targets. Hallmarks LMEs of each condition retained a distinct gene signature, but these could not be reproduced in matched lung tissue samples. Based on these gene expression signatures and unsupervised clustering, we grouped previously unclassified ILD cases into NSIP or CHP. Lastly, we characterized a gene expression pattern associated with poor outcome . Overall, our work uniquely dissects gene expression profiles between LMEs within and across different types of fibrosing ILDs. This new spatial transcriptomics approach has the potential to reclassify unclassifiable cases, to qualify the transcriptional relevance of smaller biopsies for clinical use, and to predict outcome at the time of diagnosis.
2024-09-30 | GSE255174 | GEO
Project description:Fibrosing interstitial lung diseases (ILDs) encompass a diverse range of scarring disorders that lead to progressive lung failure. Previous gene expression profiling studies focused on idiopathic pulmonary fibrosis (IPF) and bulk tissue samples. We employed digital spatial profiling to gain new insights into the spatial resolution of gene expression across distinct lung microenvironments (LMEs) in IPF, chronic hypersensitivity pneumonitis (CHP) and non-specific interstitial pneumonia (NSIP). We identified differentially expressed genes between LMEs within each condition, and across histologically similar regions between conditions. Uninvolved areas in IPF and CHP were remarkably distinct from normal controls, and displayed potential therapeutic targets. Hallmarks LMEs of each condition retained a distinct gene signature, but these could not be reproduced in matched lung tissue samples. Based on these gene expression signatures and unsupervised clustering, we grouped previously unclassified ILD cases into NSIP or CHP. Lastly, we characterized a gene expression pattern associated with poor outcome . Overall, our work uniquely dissects gene expression profiles between LMEs within and across different types of fibrosing ILDs. This new spatial transcriptomics approach has the potential to reclassify unclassifiable cases, to qualify the transcriptional relevance of smaller biopsies for clinical use, and to predict outcome at the time of diagnosis.
2024-09-30 | GSE255173 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-06-02 | GSE264233 | GEO
Project description:The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis. A comprehensively integrative approach was used to construct a global gene regulatory network based on the perturbation of key regulatory elements, transcriptional factors and miRNAs. The data also demonstrated that several subnetworks were significantly associated with key molecules involved in the diseases. We present a broad overview of the disease at a molecular level and discuss several possibly key regulatory molecular circuits that could play central roles in facilitating the progression of ILDs. Lung tissue samples from 23 patients with IPF or related disorders were obtained from the Lung Tissue Research Consortium (www.ltrcpublic.org). 11 samples came from patients who had been diagnosed with usual interstitial pneumonia/ idiopathic pulmonary fibrosis (UIP/IPF), 5 samples came from patients with non-specific interstitial pneumonia (NSIP), the remaining from patients with uncharacterized fibrosis and from patients with other ILD variants. B. Biopsies from uninvolved lung tissue from lung cancer patients (5 samples) and from one lung transplant patient were used as controls for comparison with the ILD samples.
2011-03-24 | E-GEOD-21369 | biostudies-arrayexpress
Project description:The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis. A comprehensively integrative approach was used to construct a global gene regulatory network based on the perturbation of key regulatory elements, transcriptional factors and miRNAs. The data also demonstrated that several subnetworks were significantly associated with key molecules involved in the diseases. We present a broad overview of the disease at a molecular level and discuss several possibly key regulatory molecular circuits that could play central roles in facilitating the progression of ILDs. Lung tissue samples from thirty patients with IPF or related disorders were obtained from the Lung Tissue Research Consortium (www.ltrcpublic.org). Ten samples came from patients who had been diagnosed with usual interstitial pneumonia/ idiopathic pulmonary fibrosis (UIP/IPF), nine samples came from patients with non-specific interstitial pneumonia (NSIP), four from patients with uncharacterized fibrosis, and the remaining samples came from patients with other ILD variants. Biopsies from uninvolved lung tissue from lung cancer patients (5 samples) and from one lung transplant patient were used as controls for comparison with the ILD samples.
2011-04-19 | E-GEOD-21394 | biostudies-arrayexpress
Project description:Pulmonary fibrosis (PF) is a chronic, progressive condition that represents the end-stage of many interstitial lung diseases (ILDs). Single-cell transcriptomic studies have revealed disease-emergent epithelial, fibroblast, and macrophage cell types/states in PF lungs, but the spatial contexts wherein these cells contribute to disease pathogenesis has remained uncertain. Using image-based spatial transcriptomics to profile gene expression changes in-situ across 28 lung samples from control and PF lungs, we characterized the expression of 343 genes in over 1 million nuclei at subcellular resolution. Using both cell-based and cell-agnostic approaches, we observed a diversity of distinct molecularly-defined spatial niches in control and PF lungs. Overlaying these computationally-defined niches with disease-associated histopathologic features, we identified novel patterns of dysregulation in alveoli informed by spatial context. We computationally segmented individual air spaces and using cell composition, we ordered airspaces from homeostatic to most dysregulated. Using this ordering we identified a series of stepwise molecular changes associated with progressive distal lung remodeling. Together, these results advance our understanding of the molecular programs underlying progressive PF.
2024-09-12 | GSE276934 | GEO
Project description:In this proof-of-concept study, spatial transcriptomics combined with public single-cell RNA sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathological states by examining biopsies classified across non-rejection, T cell-mediated acute rejection, and interstitial fibrosis and tubular atrophy (IFTA). Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune-cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than did tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies, and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology.
2024-05-02 | GSE245870 | GEO
Project description:The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis. A comprehensively integrative approach was used to construct a global gene regulatory network based on the perturbation of key regulatory elements, transcriptional factors and miRNAs. The data also demonstrated that several subnetworks were significantly associated with key molecules involved in the diseases. We present a broad overview of the disease at a molecular level and discuss several possibly key regulatory molecular circuits that could play central roles in facilitating the progression of ILDs.
2011-04-19 | GSE21394 | GEO
Project description:The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis. A comprehensively integrative approach was used to construct a global gene regulatory network based on the perturbation of key regulatory elements, transcriptional factors and miRNAs. The data also demonstrated that several subnetworks were significantly associated with key molecules involved in the diseases. We present a broad overview of the disease at a molecular level and discuss several possibly key regulatory molecular circuits that could play central roles in facilitating the progression of ILDs.
2011-03-25 | GSE21369 | GEO