Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury
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....
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725000191 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832540401108516864 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Ali Khadim |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7ade422744a24b8e88accc3d250ab24c |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-7ade422744a24b8e88accc3d250ab24c2025-02-05T04:31:48ZengElsevierCell Reports2211-12472025-02-01442115248Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injuryAli Khadim0Georgios Kiliaris1Ana Ivonne Vazquez-Armendariz2Tara Procida-Kowalski3David Glaser4Marek Bartkuhn5Tanya Malik6Xuran Chu7Alena Moiseenko8Irina Kuznetsova9Negah Ahmadvand10Arun Lingampally11Stefan Hadzic12Ioannis Alexopoulos13Yuexin Chen14Andreas Günther15Jürgen Behr16Jens Neumann17Herbert B. Schiller18Xiaokun Li19Norbert Weissmann20Thomas Braun21Werner Seeger22Malgorzata Wygrecka23Rory E. Morty24Susanne Herold25Elie El Agha26Department 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, GermanyDepartment 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, GermanyDepartment 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, GermanyCardio-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, GermanyCardio-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, GermanyCardio-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, GermanyDepartment 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, GermanyCardio-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, ChinaImmunology and Respiratory Department, Boehringer Ingelheim Pharma GmbH, Biberach 88400, GermanyDepartment 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, GermanyDepartment of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USADepartment 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, GermanyCardio-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, GermanyDepartment 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, GermanyResearch 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, GermanyCardio-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, GermanyInstitute of Experimental Pneumology, LMU University Hospital, Ludwig-Maximilians University, 80336 Munich, GermanyDepartment of Medicine V, LMU University Hospital, LMU Munich, Comprehensive Pneumology Center, German Center for Lung Research (DZL), 80336 Munich, GermanyResearch 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, GermanyOujiang 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, ChinaCardio-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, GermanyMax Planck Institute for Heart and Lung Research, W.G. Kerckhoff Institute, 61231 Bad Nauheim, GermanyCardio-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, GermanyCardio-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, GermanyDepartment of Translational Pulmonology, Heidelberg University Hospital, 69117 Heidelberg, GermanyDepartment 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, GermanyDepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124725000191CP: Stem cell research |
| spellingShingle | 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 Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury Cell Reports CP: Stem cell research |
| title | Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury |
| title_full | Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury |
| title_fullStr | Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury |
| title_full_unstemmed | Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury |
| title_short | Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury |
| title_sort | myofibroblasts emerge during alveolar regeneration following influenza virus induced lung injury |
| topic | CP: Stem cell research |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725000191 |
| work_keys_str_mv | AT alikhadim myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT georgioskiliaris myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT anaivonnevazquezarmendariz myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT taraprocidakowalski myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT davidglaser myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT marekbartkuhn myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT tanyamalik myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT xuranchu myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT alenamoiseenko myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT irinakuznetsova myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT negahahmadvand myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT arunlingampally myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT stefanhadzic myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT ioannisalexopoulos myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT yuexinchen myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT andreasgunther myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT jurgenbehr myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT jensneumann myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT herbertbschiller myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT xiaokunli myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT norbertweissmann myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT thomasbraun myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT wernerseeger myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT malgorzatawygrecka myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT roryemorty myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT susanneherold myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury AT elieelagha myofibroblastsemergeduringalveolarregenerationfollowinginfluenzavirusinducedlunginjury |