Spatial single-cell atlas reveals regional variations in healthy and diseased human lung
Integration of scRNA-seq data from millions of cells revealed a high diversity of cell types in the healthy and diseased human lung. In a large and complex organ, constantly exposed to external agents, it is crucial to understand the influence of lung tissue topography or external factors on gene expression variability within cell types. Here, we apply three spatial transcriptomics approaches, to: (i) localize the majority of lung cell types, including rare epithelial cells within the tissue topography, (ii) describe consistent anatomical and regional gene expression variability within and across cell types, and (iii) reveal distinct cellular neighborhoods in specific anatomical regions and examine gene expression variations in them. We thus provide a spatially resolved tissue reference atlas in three representative regions of the healthy human lung. We further demonstrate its utility by defining previously unknown imbalances of epithelial cell type compositions in chronic obstructive pulmonary disease lungs. Our topographic atlas enables a precise description of characteristic regional cellular responses upon experimental perturbations or during disease progression.
Authors
- Mats F. Nilsson (ORCID: https://orcid.org/0000-0001-9985-0387)
- Tamás Balassa
- Yuexin Chen (ORCID: https://orcid.org/0000-0001-6280-4918)
- Andreas Liontos (ORCID: https://orcid.org/0000-0003-0838-3571)
- Leire Alonso Galicia (ORCID: https://orcid.org/0000-0001-8437-1332)
- Sergio Marco Salas (ORCID: https://orcid.org/0000-0002-4636-0322)
- Xesús M. Abalo (ORCID: https://orcid.org/0000-0002-1643-0705)
- Alexandra B. Firsova (ORCID: https://orcid.org/0000-0002-7345-7429)
- Martijn C. Nawijn (ORCID: https://orcid.org/0000-0003-3372-6521)
- Krishnaa T. A. Mahbubani (ORCID: https://orcid.org/0000-0002-1327-2334)
- Jonas Theelke (ORCID: https://orcid.org/0000-0002-5074-1793)
- Žaneta Andrusivová (ORCID: https://orcid.org/0000-0002-4350-2524)
- Péter Horváth (ORCID: https://orcid.org/0000-0001-7149-4173)
- Wim Timens (ORCID: https://orcid.org/0000-0002-4146-6363)
- Christos Samakovlis (ORCID: https://orcid.org/0000-0002-9153-6040)
- Alexandros Sountoulidis (ORCID: https://orcid.org/0000-0002-8837-4642)
- Janine Gote-Schniering (ORCID: https://orcid.org/0000-0001-7869-4936)
- Malte D. Luecken (ORCID: https://orcid.org/0000-0001-7464-7921)
- Joakim Lundeberg (ORCID: https://orcid.org/0000-0003-4313-1601)
- Mircea-Gabriel Stoleriu
- Jürgen Behr (ORCID: https://orcid.org/0000-0002-9151-4829)
- Louis B. Kuemmerle
- Ludvig Larsson (ORCID: https://orcid.org/0000-0003-4209-2911)
- Fabian Joachim Theis (ORCID: https://orcid.org/0000-0002-2419-1943)
- Herbert B. Schiller (ORCID: https://orcid.org/0000-0003-1914-3215)
- Ferenc Kovács (ORCID: https://orcid.org/0000-0003-4512-4448)
- Kerstin B. Meyer (ORCID: https://orcid.org/0000-0001-5906-1498)
Institutions
- University of Bern (CH)
- University Medical Center Groningen (NL)
- University of Helsinki (FI)
- Stockholm University (SE)
- University of Groningen (NL)
- University of Cambridge (GB)
- Science for Life Laboratory (SE)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- University Hospital of Bern (CH)
- Wellcome Sanger Institute (GB)
- Helmholtz Zentrum München (DE)
- Finland University (FI)
- Asklepios Fachkliniken München-Gauting (DE)
- German Center for Lung Research (DE)
- Wenner-Gren Foundations (SE)
- Institute for Molecular Medicine Finland (FI)
- Asklepios (DE)
- Technical University of Munich (DE)
- Ludwig-Maximilians-Universität München (DE)
- KTH Royal Institute of Technology (SE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1038/s41467-025-65704-0
- Citations
- 3
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Hungarian Scientific Research Fund
- Javna Agencija za Raziskovalno Dejavnost RS
- Ludwig-Maximilians-Universität München
- Stockholms Universitet