ArticleNature communications2020
Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis.
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Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 494 papers.
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494 citing papers in PubMed, 713 citations in OpenAlex.
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- RNA Modifications as Molecular Regulators of Alveolar Epithelial Injury and Aberrant Repair in Pulmonary Fibrosis.Biomolecules · 2026Review
- Early cell-autonomous and niche-mediated epithelial response to influenza infection in primary alveolar organoids.JCI insight · 2026Article
- Sustained YAP/TAZ activation promotes aberrant alveolar epithelial cell differentiation and drives persistent fibrotic remodeling.JCI insight · 2026Article
- Effects of LATS1/2 kinases inhibition on lung epithelial cells in a regeneration model.Molecular and cellular biochemistry · 2026Article
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434 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 7 institutions in 2 countries.
Maximilian Strunz *Institute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
Lukas M Simon *Institute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.
Meshal AnsariInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.ORCID http://orcid.org/0000-0002-8819-7965
Jaymin J KathiriyaBiomedical Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1807-8570
Ilias AngelidisInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.ORCID http://orcid.org/0000-0002-0549-8878
Christoph H MayrInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
George TsidiridisInstitute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.
Marius LangeInstitute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.ORCID http://orcid.org/0000-0002-4846-1266
Laura F MattnerInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
Min YeeDepartment of Pediatrics, University of Rochester, Rochester, NY, USA.
Paulina OgarInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
Arunima SenguptaInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
Igor KukhtevichInstitute of Functional Epigenetics, Helmholtz Zentrum München, Munich, Germany.
Robert SchneiderInstitute of Functional Epigenetics, Helmholtz Zentrum München, Munich, Germany.
Zhongming ZhaoCenter for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-3477-0914
Carola VossInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.ORCID http://orcid.org/0000-0001-5243-4415
Tobias StoegerInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.ORCID http://orcid.org/0000-0002-2790-0389
Jens H L NeumannInstitute of Pathology, Ludwig Maximilians University Hospital Munich, Munich, Germany.
Anne HilgendorffInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
Jürgen BehrInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.
Michael O'ReillyDepartment of Pediatrics, University of Rochester, Rochester, NY, USA.
Mareike LehmannComprehensive Pneumology Center (CPC), Research Unit Lung Repair and Regeneration, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.ORCID http://orcid.org/0000-0002-8601-8206
Gerald BurgstallerInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany.ORCID http://orcid.org/0000-0002-7121-2567
Melanie KönigshoffComprehensive Pneumology Center (CPC), Research Unit Lung Repair and Regeneration, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
Harold A ChapmanBiomedical Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-5280-5527
Fabian J TheisInstitute of Computational Biology, Helmholtz Zentrum München, Munich, Germany. fabian.theis@helmholtz-muenchen.de.ORCID http://orcid.org/0000-0002-2419-1943
Herbert B SchillerInstitute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum Muenchen, Member of the German Center for Lung Research (DZL), Munich, Germany. herbert.schiller@helmholtz-muenchen.de.ORCID http://orcid.org/0000-0001-9498-7034
German Center for Lung Research · DEHelmholtz Zentrum München · DEUniversity of California, San Francisco · USUniversity of Rochester · USAsklepios Fachkliniken München-Gauting · DELudwig-Maximilians-Universität München · DEThe University of Texas Health Science Center at Houston · US
Funding
Program to promote lung regeneration and block fibrosisR35HL150767 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAPMAN, HAROLD A · 2020 to 2025
$5.8MEffect of Neonatal Hyperoxia on Alveolar Development and InfectionR01HL091968 · NHLBI · UNIVERSITY OF ROCHESTER · PI O'REILLY, MICHAEL A · 2009 to 2021
$5.4MInterferon-mediated in vitro and in vivo Regulation of Airway Progenitor Cells in Regeneration of Functional AlveoliF32HL143931 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KATHIRIYA, JAYMIN J · 2019 to 2020
$118kNHLBI NIH HHS F32 HL143931NHLBI NIH HHS R01 HL091968NHLBI NIH HHS R35 HL150767
Abstract
The cell type specific sequences of transcriptional programs during lung regeneration have remained elusive. Using time-series single cell RNA-seq of the bleomycin lung injury model, we resolved transcriptional dynamics for 28 cell types. Trajectory modeling together with lineage tracing revealed that airway and alveolar stem cells converge on a unique Krt8 + transitional stem cell state during alveolar regeneration. These cells have squamous morphology, feature p53 and NFkB activation and display transcriptional features of cellular senescence. The Krt8+ state appears in several independent models of lung injury and persists in human lung fibrosis, creating a distinct cell-cell communication network with mesenchyme and macrophages during repair. We generated a model of gene regulatory programs leading to Krt8+ transitional cells and their terminal differentiation to alveolar type-1 cells. We propose that in lung fibrosis, perturbed molecular checkpoints on the way to terminal differentiation can cause aberrant persistence of regenerative intermediate stem cell states.
Indexed as
RegenerationAlveolar Epithelial CellsAnimalsCell CommunicationDisease Models, AnimalFemaleGene Expression ProfilingHumansKeratin-8Lung InjuryMiceMice, Inbred C57BLPulmonary AlveoliPulmonary FibrosisSingle-Cell AnalysisStem CellsKeratin-8KRT8 protein, human
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.