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…

• NH
  National Health and Medical Research Council

  Awards: GNT1162829, GNT1195595
• NH
  National Heart, Lung, and Blood Institute

  Awards: P01HL092870, R01HL160551, HL158906, R01HL145372, U01HL175444, HL126176
• NH
  National Human Genome Research Institute

  Award: R01HG011886
• CD
  Congressionally Directed Medical Research Programs

  Award: W81XWH1910415