Spatial Transcriptomic Characterization of Novel Pathologic Niches in IPF

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

ABSTRACT An unmet medical need persists in Idiopathic Pulmonary fibrosis (IPF), for which treatments additional to anti-fibrotic therapy are needed. Single cell RNA sequencing (scRNA-seq) has advanced our understanding of IPF with cell type-specific insights but lacks cellular tissue context. Spatial transcriptomics addresses this by providing spatially resolved gene expression, enabling gene and cell type localization within the tissue environment. We profiled IPF and control patient lung tissue sections using spatial transcriptomics and combined the data with an atlas of integrated IPF scRNA-seq datasets. Through computational analysis, we identified three disease-associated pathologic niches with unique cellular composition / localization and analyzed their cell-cell communication. We identified the Fibrotic niche, comprising Myofibroblasts and Aberrant Basaloid cells, preferentially located around airways and close to the Airway Macrophage niche in the lumen, containing SPP1+ Macrophages. We also identified the Immune niche, distinct foci of lymphoid cells in fibrotic tissue, surrounded by remodeled endothelial vessels. TEASER Spatial transcriptomics localizes genes and cell types in the tissue and identifies pathological cellular niches in IPF and control lungs.

Authors 13

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;

   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;

   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

   3 Boehringer Ingelheim Pharma GmbH & Co. KG, Department Drug Discovery Sciences, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany;

   Boehringer Ingelheim Pharma GmbH & Co. KG, Department Drug Discovery Sciences, Birkendorfer Strasse 65, 8897 Biberach an der Riss, Germany

4. Charlotte Lempp

   Boehringer Ingelheim (Germany)

   Affiliation as printed

   3 Boehringer Ingelheim Pharma GmbH & Co. KG, Department Drug Discovery Sciences, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany;

   Boehringer Ingelheim Pharma GmbH & Co. KG, Department Drug Discovery Sciences, Birkendorfer Strasse 65, 8897 Biberach an der Riss, Germany

5. 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), Institute of Pathology, Hannover Medical School, Hannover, Germany;

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Institute of Pathology, Hannover Medical School, Hannover, Germany

6. 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), Institute of Pathology, Hannover Medical School, Hannover, Germany;

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Institute of Pathology, Hannover Medical School, Hannover, Germany

7. 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),Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany;

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL),Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany

8. Danny David Jonigk Aachen German Center for Lung Research (DZL) Institute of Pathology, Hannover Medical School Institute of Pathology, University Medical Center

   Medizinische Hochschule Hannover · 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), Institute of Pathology, Hannover Medical School, Institute of Pathology, University Medical Center RWTH University of Aachen, Germany;

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Institute of Pathology, Hannover Medical School, Institute of Pathology, University Medical Center RWTH University of Aachen, Germany

9. Mark Kühnel Aachen Institute of Pathology, University Medical Center German Center for Lung Research (DZL) 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)

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

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Institute of Pathology, University Medical Center RWTH University of Aachen, Aachen, Germany

10. 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

    Boehringer Ingelheim Pharma GmbH & Co. KG, Department Drug Discovery Sciences, Birkendorfer Strasse 65, 397 Biberach an der Riss, Germany

11. 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;

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

12. Fidel Ramírez

    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;

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

13. Matthew James Thomas

    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;

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