Academic Journal
Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice.
| Title: | Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice. |
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| Authors: | Kusumoto T; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; Japan Society for the Promotion of Science, Tokyo, Japan., Yotsukura M; Japan Society for the Promotion of Science, Tokyo, Japan; Division of Thoracic Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan; Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan., Asakura T; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Namkoong H; Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan., Ogawa T; Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine National Defense Medical College, Saitama, Japan., Hegab AE; Medical Education Center, International University of Health and Welfare, Narita, Japan., Nakatake Y; Department of Systems Medicine, Keio University School of Medicine, Tokyo, Japan., Oda M; Department of Integrated Medicine and Biochemistry, Keio University School of Medicine, Tokyo, Japan., Saito F; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Kamata H; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan., Hamamoto J; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Okamori S; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Seki M; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan., Suzuki Y; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan., Hasegawa N; Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan., Asamura H; Division of Thoracic Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan., Watanabe H; Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Ko MSH; Department of Systems Medicine, Keio University School of Medicine, Tokyo, Japan., Ieda M; Department of Cardiology, Keio University School of Medicine, Tokyo, Japan., Fukunaga K; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan., Ishii M; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: ishii.makoto.d3@f.mail.nagoya-u.ac.jp. |
| Source: | Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2025 Sep 08; Vol. 778, pp. 152384. Date of Electronic Publication: 2025 Jul 17. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2002- >: San Diego, CA : Elsevier Original Publication: New York, Academic Press. |
| MeSH Terms: | Epithelial Cells*/cytology , Epithelial Cells*/metabolism , Lung*/cytology , Lung*/pathology , Lung*/virology , Orthomyxoviridae Infections*/virology , Orthomyxoviridae Infections*/pathology , Orthomyxoviridae Infections*/therapy , Orthomyxoviridae Infections*/complications , Lung Injury*/virology , Lung Injury*/therapy , Lung Injury*/pathology , Acute Lung Injury*/virology , Acute Lung Injury*/therapy , Acute Lung Injury*/pathology , Cellular Reprogramming*, Fibroblasts/cytology ; Fibroblasts/metabolism ; Alveolar Epithelial Cells/metabolism ; Transcription Factors/metabolism ; Animals ; Mice ; Mice, Inbred C57BL |
| Abstract: | We recently reported that a combination of four transcription factors (Nkx2-1, Foxa1, Foxa2, and Gata6) directly reprograms mouse embryonic fibroblasts (MEFs) into differentiated self-renewable alveolar epithelial-like cells in a serum-free 3D organoid system. Here, we aimed to generate induced pulmonary epithelial-like cells in serum-containing culture (iPULsSC) using the same four transcription factors in a serum-containing 3D culture system. We found that the global gene expression profile of iPULsSC was similar to that of alveolar epithelial type II (AT2) and alveolar type I (AT1) cells. Surfactant protein (SP)-C-positive iPULsSC displayed lamellar body-like structures, consistent with the features of AT2 cells. Furthermore, we provide evidence that intratracheal administration of iPULsSC rescued influenza virus-induced acute lung injury in mice. These findings suggest that iPULsSC can provide a potential source of lung epithelial cells for regenerative medicine. Reprogramming fibroblasts using serum-containing media, besides previously established serum-free systems, can provide a potential source of lung epithelial cells. (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Makoto Ishii reports financial support was provided by Japan Agency for Medical Research and Development (AMED), JSPS KAKENHI, the Takeda Science Foundation, and the Ichiro Kanehara Foundation. Makoto Ishii has patent #U.S. Patent No. 11,718,831 B2, Japanese Patent No. 7361963 licensed to Nagoya University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Alveolar epithelial cells; Cell therapy; Direct reprogramming; Influenza; Surfactant protein (SP)–C |
| Molecular Sequence: | GEO GSE109810; GSE133694 |
| Substance Nomenclature: | 0 (Transcription Factors) |
| Entry Date(s): | Date Created: 20250723 Date Completed: 20250826 Latest Revision: 20260325 |
| Update Code: | 20260326 |
| DOI: | 10.1016/j.bbrc.2025.152384 |
| PMID: | 40700809 |
| Database: | MEDLINE |
| ISSN: | 1090-2104 |
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| DOI: | 10.1016/j.bbrc.2025.152384 |