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Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis [Xenium]

ABSTRACT: Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis [Xenium]

PROVIDER: PRJNA1056041 | ENA |

REPOSITORIES: ENA

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Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis [Xenium]

Project description:Large-scale changes in the structure and cellular makeup of the distal lung are a hallmark of pulmonary fibrosis (PF), but the spatial contexts that contribute to disease pathogenesis have remained uncertain. Using image-based spatial transcriptomics, we analyzed the gene expression of 1.6 million cells from 35 unique lungs. Through complementary cell-based and innovative cell-agnostic analyses, we characterized the localization of PF-emergent cell types, established the cellular and molecular basis of classical PF histopathologic features and identified a diversity of distinct molecularly defined spatial niches in control and PF lungs. Using machine learning and trajectory analysis to segment and rank airspaces on a gradient of remodeling severity, we identified compositional and molecular changes associated with progressive distal lung pathology, beginning with alveolar epithelial dysregulation and culminating with changes in macrophage polarization. Together, these results provide a unique, spatially resolved view of PF and establish methods that could be applied to other spatial transcriptomic studies.

2024-06-04 | GSE250346 | GEO

Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis

Project description:Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis

| PRJNA1159772 | ENA

Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis [Visium]

Project description:Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis [Visium]

| PRJNA1160022 | ENA

Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis [Visium]

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

Selective remodelling of the adipose niche in obesity and weight loss [Xenium]

Project description:Selective remodelling of the adipose niche in obesity and weight loss [Xenium]

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Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis.

Project description:The human lung is structurally complex, with a diversity of specialized epithelial, stromal and immune cells playing specific functional roles in anatomically distinct locations, and large-scale changes in the structure and cellular makeup of this distal lung is a hallmark of pulmonary fibrosis (PF) and other progressive chronic lung diseases. Single-cell transcriptomic studies have revealed numerous disease-emergent/enriched cell types/states in PF lungs, but the spatial contexts wherein these cells contribute to disease pathogenesis has remained uncertain. Using sub-cellular resolution image-based spatial transcriptomics, we analyzed the gene expression of more than 1 million cells from 19 unique lungs. Through complementary cell-based and innovative cell-agnostic analyses, we characterized the localization of PF-emergent cell-types, established the cellular and molecular basis of classical PF histopathologic disease features, and identified a diversity of distinct molecularly-defined spatial niches in control and PF lungs. Using machine-learning and trajectory analysis methods to segment and rank airspaces on a gradient from normal to most severely remodeled, we identified a sequence of compositional and molecular changes that associate with progressive distal lung pathology, beginning with alveolar epithelial dysregulation and culminating with changes in macrophage polarization. Together, these results provide a unique, spatially-resolved characterization of the cellular and molecular programs of PF and control lungs, provide new insights into the heterogeneous pathobiology of PF, and establish analytical approaches which should be broadly applicable to other imaging-based spatial transcriptomic studies.

| S-EPMC10760144 | biostudies-literature

Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-09-12 | GSE276945 | GEO

A niche-dependent redox rheostat regulates epithelial stem cell fate in the distal colon

Project description:The niche environment surrounding intestinal stem cells (ISCs) varies along the length of intestine and provides key cues that regulate stem cell fate. Here, we investigated the role of cellular redox balance in colonic ISC function. We show that hypoxia and Wnt signaling synergize to restrict the reactive oxygen species (ROS) generating enzyme NADPH oxidase 1 (NOX1) to the crypt base in the distal colon. NOX1 function maintains a more oxidative cell state that licenses cell cycle entry, altering the balance of asymmetric stem cell self-renewal and directing lineage commitment. Mechanistically, cell redox state directs a self-reinforcing circuit that connects hypoxia inducible factor 1 (HIF1a)-dependent signaling with regulation of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1). Our studies show that cellular redox balance is a central and niche-dependent regulator of epithelial homeostasis and regeneration and provide a basis for understanding disease propensity in the distal large intestine.

2025-02-17 | GSE289209 | GEO

A niche-dependent redox rheostat regulates epithelial stem cell fate in the distal colon II

2025-02-17 | GSE289397 | GEO

Xenium

Project description:Xenium

2025-01-24 | OEX00030219 | NODE