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doi:10.22028/D291-41773
Titel: | Mutual Regulation of Transcriptomes between Murine Pneumocytes and Fibroblasts Mediates Alveolar Regeneration in Air-Liquid Interface Cultures |
VerfasserIn: | Yao, Yiwen Miethe, Sarah Kattler, Kathrin Colakoglu, Betül Walter, Jörn Schneider-Daum, Nicole Herr, Christian Garn, Holger Ritzmann, Felix Bals, Robert Beisswenger, Christoph |
Sprache: | Englisch |
Titel: | American Journal of Respiratory Cell and Molecular Biology |
Bandnummer: | 70 (2024) |
Heft: | 3 |
Verlag/Plattform: | American Thoracic Society |
Erscheinungsjahr: | 2023 |
Freie Schlagwörter: | alveolar regeneration pneumocytes fibroblasts IL-6 single-cell |
DDC-Sachgruppe: | 500 Naturwissenschaften 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Alveolar type 2 and club cells are part of the stem cell niche of the lung and their differentiation is required for pulmonary homeostasis and tissue regeneration. A disturbed crosstalk between fibroblasts and epithelial cells contributes to the loss of lung structure in chronic lung diseases. Therefore, it is important to understand how fibroblasts and lung epithelial cells interact during regeneration. Here, we analyzed the interaction of fibroblasts and the alveolar epithelium modeled in air–liquid interface cultures. Single-cell transcriptomics showed that cocultivation with fibroblasts leads to increased expression of type 2 markers in pneumocytes, activation of regulons associated with the maintenance of alveolar type 2 cells (e.g., Etv5), and transdifferentiation of club cells toward pneumocytes. This was accompanied by an intensified transepithelial barrier. Vice versa, the activation of NF-κB pathways and the CEBPB regulon and the expression of IL-6 and other differentiation factors (e.g., fibroblast growth factors) were increased in fibroblasts cocultured with epithelial cells. Recombinant IL-6 enhanced epithelial barrier formation. Therefore, in our coculture model, regulatory loops were identified by which lung epithelial cells mediate regeneration and differentiation of the alveolar epithelium in a cooperative manner with the mesenchymal compartment. |
DOI der Erstveröffentlichung: | 10.1165/rcmb.2023-0078OC |
URL der Erstveröffentlichung: | https://doi.org/10.1165/rcmb.2023-0078OC |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-417739 hdl:20.500.11880/37378 http://dx.doi.org/10.22028/D291-41773 |
ISSN: | 1535-4989 1044-1549 |
Datum des Eintrags: | 18-Mär-2024 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplements |
In Beziehung stehendes Objekt: | https://www.atsjournals.org/doi/suppl/10.1165/rcmb.2023-0078OC/suppl_file/disclosures.pdf https://www.atsjournals.org/doi/suppl/10.1165/rcmb.2023-0078OC/suppl_file/yao_data_supplement.pdf |
Fakultät: | M - Medizinische Fakultät NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | M - Innere Medizin NT - Biowissenschaften |
Professur: | M - Prof. Dr. Robert Bals NT - Prof. Dr. Jörn Walter |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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