Mesenchymal-Epithelial Interactome Analysis Reveals Essential Factors Required for Fibroblast-Free Alveolosphere Formation
Summary: Lung epithelial cells and fibroblasts are key cell populations in lung development. Fibroblasts support type 2 alveolar epithelial cells (AEC2) in the developing and mature lung. However, fibroblast-AEC2 interactions have not been clearly described. We addressed this in the present study by...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-01-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004218302529 |
| _version_ | 1828336233940516864 |
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| author | Kazushige Shiraishi Shigeyuki Shichino Satoshi Ueha Takuya Nakajima Shinichi Hashimoto Satoshi Yamazaki Kouji Matsushima |
| author_facet | Kazushige Shiraishi Shigeyuki Shichino Satoshi Ueha Takuya Nakajima Shinichi Hashimoto Satoshi Yamazaki Kouji Matsushima |
| author_sort | Kazushige Shiraishi |
| collection | DOAJ |
| description | Summary: Lung epithelial cells and fibroblasts are key cell populations in lung development. Fibroblasts support type 2 alveolar epithelial cells (AEC2) in the developing and mature lung. However, fibroblast-AEC2 interactions have not been clearly described. We addressed this in the present study by time course serial analysis of gene expression sequencing (SAGE-seq) of epithelial cells and fibroblasts of developing and mature murine lungs. We identified lung fibroblast-epithelial interactions that potentially regulate alveologenesis and are mediated by fibroblast-expressed ligands and epithelial cell surface receptors. In the epithelial-fibroblast co-culture alveolosphere formation assay, single intervention against fibroblast-expressed ligand or associated signaling cascades promoted or inhibited alveolosphere growth. Adding the ligand-associated molecules fibroblast growth factor 7 and Notch ligand and inhibitors of bone morphogenetic protein 4, transforming growth factor β, and glycogen synthase kinase-3β to the culture medium enabled fibroblast-free alveolosphere formation. The results revealed the essential factors regulating fibroblast-AEC2 interactions. : Molecular Interaction; Developmental Biology; Transcriptomics Subject Areas: Molecular Interaction, Developmental Biology, Transcriptomics |
| first_indexed | 2024-04-13T21:58:07Z |
| format | Article |
| id | doaj.art-33ad791a9d6c4f04acd52c8bc7dd4f79 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-13T21:58:07Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-33ad791a9d6c4f04acd52c8bc7dd4f792022-12-22T02:28:12ZengElsevieriScience2589-00422019-01-0111318333Mesenchymal-Epithelial Interactome Analysis Reveals Essential Factors Required for Fibroblast-Free Alveolosphere FormationKazushige Shiraishi0Shigeyuki Shichino1Satoshi Ueha2Takuya Nakajima3Shinichi Hashimoto4Satoshi Yamazaki5Kouji Matsushima6Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Noda 278-0022, JapanDepartment of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Noda 278-0022, JapanDepartment of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Noda 278-0022, JapanDepartment of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Noda 278-0022, JapanDepartment of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Noda 278-0022, Japan; Department of Integrative Medicine for Longevity, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, JapanDivision of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, JapanDepartment of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Noda 278-0022, Japan; Corresponding authorSummary: Lung epithelial cells and fibroblasts are key cell populations in lung development. Fibroblasts support type 2 alveolar epithelial cells (AEC2) in the developing and mature lung. However, fibroblast-AEC2 interactions have not been clearly described. We addressed this in the present study by time course serial analysis of gene expression sequencing (SAGE-seq) of epithelial cells and fibroblasts of developing and mature murine lungs. We identified lung fibroblast-epithelial interactions that potentially regulate alveologenesis and are mediated by fibroblast-expressed ligands and epithelial cell surface receptors. In the epithelial-fibroblast co-culture alveolosphere formation assay, single intervention against fibroblast-expressed ligand or associated signaling cascades promoted or inhibited alveolosphere growth. Adding the ligand-associated molecules fibroblast growth factor 7 and Notch ligand and inhibitors of bone morphogenetic protein 4, transforming growth factor β, and glycogen synthase kinase-3β to the culture medium enabled fibroblast-free alveolosphere formation. The results revealed the essential factors regulating fibroblast-AEC2 interactions. : Molecular Interaction; Developmental Biology; Transcriptomics Subject Areas: Molecular Interaction, Developmental Biology, Transcriptomicshttp://www.sciencedirect.com/science/article/pii/S2589004218302529 |
| spellingShingle | Kazushige Shiraishi Shigeyuki Shichino Satoshi Ueha Takuya Nakajima Shinichi Hashimoto Satoshi Yamazaki Kouji Matsushima Mesenchymal-Epithelial Interactome Analysis Reveals Essential Factors Required for Fibroblast-Free Alveolosphere Formation iScience |
| title | Mesenchymal-Epithelial Interactome Analysis Reveals Essential Factors Required for Fibroblast-Free Alveolosphere Formation |
| title_full | Mesenchymal-Epithelial Interactome Analysis Reveals Essential Factors Required for Fibroblast-Free Alveolosphere Formation |
| title_fullStr | Mesenchymal-Epithelial Interactome Analysis Reveals Essential Factors Required for Fibroblast-Free Alveolosphere Formation |
| title_full_unstemmed | Mesenchymal-Epithelial Interactome Analysis Reveals Essential Factors Required for Fibroblast-Free Alveolosphere Formation |
| title_short | Mesenchymal-Epithelial Interactome Analysis Reveals Essential Factors Required for Fibroblast-Free Alveolosphere Formation |
| title_sort | mesenchymal epithelial interactome analysis reveals essential factors required for fibroblast free alveolosphere formation |
| url | http://www.sciencedirect.com/science/article/pii/S2589004218302529 |
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