Spatial transcriptomic characterization of pathologic niches in IPF

Science Advances, vol. 10, pp. eadl5473

Abstract

Despite advancements in antifibrotic therapy, idiopathic pulmonary fibrosis (IPF) remains a medical condition with unmet needs. Single-cell RNA sequencing (scRNA-seq) has enhanced our understanding of IPF but lacks the cellular tissue context and gene expression localization that spatial transcriptomics provides. To bridge this gap, we profiled IPF and control patient lung tissue using spatial transcriptomics, integrating the data with an IPF scRNA-seq atlas. We identified three disease-associated niches with unique cellular compositions and localizations. These include a fibrotic niche, consisting of myofibroblasts and aberrant basaloid cells, located around airways and adjacent to an airway macrophage niche in the lumen, containing SPP1 + macrophages. In addition, we identified an immune niche, characterized by distinct lymphoid cell foci in fibrotic tissue, surrounded by remodeled endothelial vessels. This spatial characterization of IPF niches will facilitate the identification of drug targets that disrupt disease-driving niches and aid in the development of disease relevant in vitro models.

Authors 17

1. Christoph H. Mayr corresponding

   Boehringer Ingelheim (Germany)

   Affiliation as printed

   Boehringer Ingelheim Pharma GmbH & Co. KG, Department Immunology and Respiratory Disease research, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany

2. Diana Santacruz

   Boehringer Ingelheim (Germany)

   Affiliation as printed

   Boehringer Ingelheim Pharma GmbH & Co. KG, Global Computational Biology and Digital Sciences, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany

3. Sebastian Jarosch

   Boehringer Ingelheim (Germany)

   Affiliation as printed

   Boehringer Ingelheim Pharma GmbH & Co. KG, Department Drug Discovery Sciences, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany

4. Marina Bleck

   Boehringer Ingelheim (United States)

   Affiliation as printed

   Boehringer Ingelheim Pharmaceuticals Inc., Department of Immunology and Respiratory Diseases Research, 900 Ridgebury Road, Ridgefield, CT 06877 USA

5. Angela McNabola

   Boehringer Ingelheim (United States)

   Affiliation as printed

   Boehringer Ingelheim Pharmaceuticals Inc., Department of Immunology and Respiratory Diseases Research, 900 Ridgebury Road, Ridgefield, CT 06877 USA

6. Charlotte Lempp

   Boehringer Ingelheim (Germany)

   Affiliation as printed

   Boehringer Ingelheim Pharma GmbH & Co. KG, Department Drug Discovery Sciences, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany

7. Lavinia Neubert

   Medizinische Hochschule Hannover · German Center for Lung Research

   Affiliation as printed

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany

   Institute of Pathology, Hannover Medical School, Hannover, Germany

8. Berenice Rath

   Medizinische Hochschule Hannover · German Center for Lung Research

   Affiliation as printed

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany

   Institute of Pathology, Hannover Medical School, Hannover, Germany

9. Jan C. Kamp

   Medizinische Hochschule Hannover · German Center for Lung Research

   Affiliation as printed

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany

   Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany

10. Danny David Jonigk Aachen Institute of Pathology, University Medical Center

    Medizinische Hochschule Hannover · Universitätsklinikum Aachen · German Center for Lung Research · RWTH Aachen University

    Affiliation as printed

    Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany

    Institute of Pathology, Hannover Medical School, Hannover, Germany

    Institute of Pathology, University Medical Center RWTH University of Aachen, Aachen, Germany

11. Mark Kühnel Aachen Institute of Pathology, University Medical Center

    Universitätsklinikum Aachen · German Center for Lung Research · RWTH Aachen University

    Affiliation as printed

    Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany

    Institute of Pathology, University Medical Center RWTH University of Aachen, Aachen, Germany

12. Holger Schlüter

    Boehringer Ingelheim (Germany)

    Affiliation as printed

    Boehringer Ingelheim Pharma GmbH & Co. KG, Department Immunology and Respiratory Disease research, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany

13. Alexander C. Klimowicz

    Boehringer Ingelheim (United States)

    Affiliation as printed

    Boehringer Ingelheim Pharmaceuticals Inc., Department of Immunology and Respiratory Diseases Research, 900 Ridgebury Road, Ridgefield, CT 06877 USA

14. Jonas Doerr

    Boehringer Ingelheim (Germany)

    Affiliation as printed

    Boehringer Ingelheim Pharma GmbH & Co. KG, Department Drug Discovery Sciences, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany

15. Alec Dick

    Boehringer Ingelheim (Germany)

    Affiliation as printed

    Boehringer Ingelheim Pharma GmbH & Co. KG, Global Computational Biology and Digital Sciences, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany

16. Fidel Ramírez corresponding

    Boehringer Ingelheim (Germany)

    Affiliation as printed

    Boehringer Ingelheim Pharma GmbH & Co. KG, Global Computational Biology and Digital Sciences, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany

17. Matthew James Thomas corresponding

    Boehringer Ingelheim (Germany)

    Affiliation as printed

    Boehringer Ingelheim Pharma GmbH & Co. KG, Department Immunology and Respiratory Disease research, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany