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Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis.

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

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Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

  • 引用：Vannan A, Lyu R, Williams AL, Negretti NM, Mee ED, Hirsh J, Hirsh S, Hadad N, Nichols DS, Calvi CL, Taylor CJ, Polosukhin VV, Serezani APM, McCall AS, Gokey JJ, Shim H, Ware LB, Bacchetta MJ, Shaver CM, Blackwell TS, Walia R, Sucre JMS, Kropski JA, McCarthy DJ, Banovich NE. (2025). Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis. Nature genetics. PMID 39901013 · PMC11906353 · DOI 10.1038/s41588-025-02080-x
  • 证据类型：PRIMARY_RESEARCH
  • 主题：rna-seq、spatial-omics
  • 被引次数（采集时）：99
  • 原始记录：[Europe PMC](https://europepmc.org/article/MED/39901013)
  • 来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

    • 作者摘要（按来源许可复用）

    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.

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    Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis. · GeniOmics