Single-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung.

Autor: Martins LR; Division of Applied Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany. leila.martins@nct-heidelberg.de.; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany. leila.martins@nct-heidelberg.de., Sieverling L; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.; Division of Translational Medical Oncology, DKFZ, Heidelberg, Germany., Michelhans M; Division of Applied Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.; Division of Translational Medical Oncology, DKFZ, Heidelberg, Germany.; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany., Schiller C; Division of Applied Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University Hospital and Heidelberg University, Heidelberg, Germany., Erkut C; Division of Applied Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany., Grünewald TGP; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.; Hopp-Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Translational Pediatric Sarcoma Research, DKFZ, Heidelberg, Germany.; Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.; German Cancer Consortium (DKTK), Heidelberg, Germany., Triana S; Structural and Computational Biology, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.; Broad Institute of Harvard and MIT, Cambridge, USA.; Department of Chemistry, Institute for Medical Engineering and Sciences (IMES), and Koch Institute for Integrative Cancer Research, MIT, Cambridge, USA., Fröhling S; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.; Division of Translational Medical Oncology, DKFZ, Heidelberg, Germany.; German Cancer Consortium (DKTK), Heidelberg, Germany.; Institute of Human Genetics, Heidelberg University, Heidelberg, Germany., Velten L; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain., Glimm H; Department for Translational Medical Oncology, National Center for Tumor Diseases Dresden (NCT/UCC), a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.; Translational Medical Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; Translational Functional Cancer Genomics, DKFZ, Heidelberg, Germany.; DKTK, partner site Dresden, Dresden, Germany., Scholl C; Division of Applied Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany. claudia.scholl@nct-heidelberg.de.; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany. claudia.scholl@nct-heidelberg.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Mar 12; Vol. 15 (1), pp. 2246. Date of Electronic Publication: 2024 Mar 12.
DOI: 10.1038/s41467-024-46469-4
Abstrakt: Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of therapeutic approaches for lung diseases. We combine mouse models allowing diphtheria toxin-mediated damage of specific epithelial cell types and parallel GFP-labeling of functionally dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncover cell types, including Krt13 + basal and Krt15 + club cells, detect an intermediate cell state between basal and goblet cells, reveal goblet cells as actively dividing progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also show that diphtheria toxin-expressing cells can persist in the lung, express specific inflammatory factors, and transcriptionally resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to concise epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions.
(© 2024. The Author(s).)
Databáze: MEDLINE
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