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Updated: Feb 11, 2026
10:16
Mining Spatial Transcriptomics Datasets using DeepSpaceDB
Published on: September 5, 2025
797
Spatial transcriptomics reveals coordinated endothelial and epithelial activator protein-1 activation in chronic lung
Yasufumi Goda1, Tatsuhiko Naito2, Mudassir M Banday1
1Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Summary
Chronic lung allograft dysfunction (CLAD) involves coordinated AP-1 activation and shared inflammatory signaling in lung grafts. Understanding these gene expression profiles offers new mechanistic insights into CLAD pathogenesis.
Area of Science:
- Pulmonary Medicine
- Immunology
- Genomics
Background:
- Chronic lung allograft dysfunction (CLAD) is a major barrier to long-term lung transplant survival.
- The precise molecular mechanisms and gene expression profiles underlying CLAD remain incompletely understood.
Purpose of the Study:
- To elucidate the gene expression landscape of CLAD using spatial transcriptomics.
- To identify key molecular pathways and cellular players involved in CLAD pathogenesis.
Main Methods:
- Spatial transcriptomic analysis of human lung tissues from CLAD patients, non-CLAD transplant recipients, and healthy controls.
- Differential gene expression analysis to identify upregulated and downregulated pathways.
- Analysis of cellular composition and signaling pathways in different compartments.
Main Results:
- AP-1 target genes (JUNB, FOS) were significantly upregulated in the epithelium and endothelium of CLAD lungs.
- Anti-fibrotic genes (A2M, SFTPA1,2) were upregulated in non-CLAD lungs.
- CLAD lungs showed a T cell-predominant lymphocyte population with elevated JAK3-IL7R signaling.
- TNF and IL-17 signaling pathways were activated in both epithelial and endothelial cells in CLAD, with JUNB and FOS as central hubs.
Conclusions:
- Coordinated AP-1 activation and shared inflammatory/fibrotic signaling across epithelial and endothelial compartments may drive CLAD.
- Both epithelial and endothelial compartments play transcriptionally active roles in CLAD pathogenesis.
- These findings provide novel mechanistic insights into CLAD development and potential therapeutic targets.
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