Cell Reports (Feb 2025)
Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury
- Ali Khadim,
- Georgios Kiliaris,
- Ana Ivonne Vazquez-Armendariz,
- Tara Procida-Kowalski,
- David Glaser,
- Marek Bartkuhn,
- Tanya Malik,
- Xuran Chu,
- Alena Moiseenko,
- Irina Kuznetsova,
- Negah Ahmadvand,
- Arun Lingampally,
- Stefan Hadzic,
- Ioannis Alexopoulos,
- Yuexin Chen,
- Andreas Günther,
- Jürgen Behr,
- Jens Neumann,
- Herbert B. Schiller,
- Xiaokun Li,
- Norbert Weissmann,
- Thomas Braun,
- Werner Seeger,
- Malgorzata Wygrecka,
- Rory E. Morty,
- Susanne Herold,
- Elie El Agha
Affiliations
- Ali Khadim
- Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany
- Georgios Kiliaris
- Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany
- Ana Ivonne Vazquez-Armendariz
- Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; University of Bonn, Transdisciplinary Research Area Life and Health, Organoid Biology, Life & Medical Sciences Institute, 53115 Bonn, Germany
- Tara Procida-Kowalski
- Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Biomedical Informatics and Systems Medicine, Justus-Liebig-University Giessen, 35392 Giessen, Germany
- David Glaser
- Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Biomedical Informatics and Systems Medicine, Justus-Liebig-University Giessen, 35392 Giessen, Germany
- Marek Bartkuhn
- Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Biomedical Informatics and Systems Medicine, Justus-Liebig-University Giessen, 35392 Giessen, Germany
- Tanya Malik
- Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany
- Xuran Chu
- Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Department of Medicine II, Internal Medicine, Pulmonary and Critical Care, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
- Alena Moiseenko
- Immunology and Respiratory Department, Boehringer Ingelheim Pharma GmbH, Biberach 88400, Germany
- Irina Kuznetsova
- Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany
- Negah Ahmadvand
- Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA
- Arun Lingampally
- Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Department of Medicine II, Internal Medicine, Pulmonary and Critical Care, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany
- Stefan Hadzic
- Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Department of Medicine II, Internal Medicine, Pulmonary and Critical Care, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany
- Ioannis Alexopoulos
- Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany
- Yuexin Chen
- Research Unit Precision Regenerative Medicine (PRM), Comprehensive Pneumology Center (CPC), German Center for Lung Research (DZL), 81377 Munich, Germany; Institute of Experimental Pneumology, LMU University Hospital, Ludwig-Maximilians University, 80336 Munich, Germany
- Andreas Günther
- Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Department of Medicine II, Internal Medicine, Pulmonary and Critical Care, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany
- Jürgen Behr
- Institute of Experimental Pneumology, LMU University Hospital, Ludwig-Maximilians University, 80336 Munich, Germany
- Jens Neumann
- Department of Medicine V, LMU University Hospital, LMU Munich, Comprehensive Pneumology Center, German Center for Lung Research (DZL), 80336 Munich, Germany
- Herbert B. Schiller
- Research Unit Precision Regenerative Medicine (PRM), Comprehensive Pneumology Center (CPC), German Center for Lung Research (DZL), 81377 Munich, Germany; Institute of Experimental Pneumology, LMU University Hospital, Ludwig-Maximilians University, 80336 Munich, Germany
- Xiaokun Li
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
- Norbert Weissmann
- Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Department of Medicine II, Internal Medicine, Pulmonary and Critical Care, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany
- Thomas Braun
- Max Planck Institute for Heart and Lung Research, W.G. Kerckhoff Institute, 61231 Bad Nauheim, Germany
- Werner Seeger
- Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Department of Medicine II, Internal Medicine, Pulmonary and Critical Care, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Max Planck Institute for Heart and Lung Research, W.G. Kerckhoff Institute, 61231 Bad Nauheim, Germany
- Malgorzata Wygrecka
- Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Department of Medicine II, Internal Medicine, Pulmonary and Critical Care, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany
- Rory E. Morty
- Department of Translational Pulmonology, Heidelberg University Hospital, 69117 Heidelberg, Germany
- Susanne Herold
- Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany
- Elie El Agha
- Department of Medicine V, Internal Medicine, Infectious Diseases and Infection Control, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany; Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Corresponding author
- Journal volume & issue
-
Vol. 44,
no. 2
p. 115248
Abstract
Summary: Alveolar regeneration requires the coordinated engagement of epithelial stem cells and mesenchymal niche cells to restore the intricate alveolar architecture of the lung. The current paradigm is that certain aspects of lung organogenesis are mimicked during injury repair in the adult stage. Here, we employ a longitudinal single-cell transcriptomic survey to fate map lung mesenchymal cells throughout development and adulthood. We show that myofibroblasts that are reminiscent of developmental alveolar myofibroblasts (AMFs), termed AMF-like cells, are activated during alveolar regeneration following influenza-virus-induced lung injury. Although AMF-like cells share a similar transcriptomic signature with myofibroblasts that are associated with aberrant repair and fibrosis, these cells do not derive from fibroblast growth factor 10-positive alveolar fibroblasts, and their dysregulation is associated with failed alveolar regeneration in humans. Our data emphasize the role played by developmental mechanisms in alveolar regeneration and highlight the context-dependent nature of myofibroblast biology and function during injury repair.
