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Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice.

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Τίτλος: Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice.
Συγγραφείς: 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.
Πηγή: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2025 Sep 08; Vol. 778, pp. 152384. Date of Electronic Publication: 2025 Jul 17.
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: 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.
Ιατρικοί όροι (MeSH): 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
Περίληψη: 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
Βάση Δεδομένων: MEDLINE
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  Data: Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice.
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  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Kusumoto+T%22&quot;&gt;Kusumoto T&lt;/searchLink&gt;; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; Japan Society for the Promotion of Science, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Yotsukura+M%22&quot;&gt;Yotsukura M&lt;/searchLink&gt;; 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.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Asakura+T%22&quot;&gt;Asakura T&lt;/searchLink&gt;; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Namkoong+H%22&quot;&gt;Namkoong H&lt;/searchLink&gt;; Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Ogawa+T%22&quot;&gt;Ogawa T&lt;/searchLink&gt;; Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine National Defense Medical College, Saitama, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Hegab+AE%22&quot;&gt;Hegab AE&lt;/searchLink&gt;; Medical Education Center, International University of Health and Welfare, Narita, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Nakatake+Y%22&quot;&gt;Nakatake Y&lt;/searchLink&gt;; Department of Systems Medicine, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Oda+M%22&quot;&gt;Oda M&lt;/searchLink&gt;; Department of Integrated Medicine and Biochemistry, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Saito+F%22&quot;&gt;Saito F&lt;/searchLink&gt;; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Kamata+H%22&quot;&gt;Kamata H&lt;/searchLink&gt;; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Hamamoto+J%22&quot;&gt;Hamamoto J&lt;/searchLink&gt;; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Okamori+S%22&quot;&gt;Okamori S&lt;/searchLink&gt;; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Seki+M%22&quot;&gt;Seki M&lt;/searchLink&gt;; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Suzuki+Y%22&quot;&gt;Suzuki Y&lt;/searchLink&gt;; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Hasegawa+N%22&quot;&gt;Hasegawa N&lt;/searchLink&gt;; Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Asamura+H%22&quot;&gt;Asamura H&lt;/searchLink&gt;; Division of Thoracic Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Watanabe+H%22&quot;&gt;Watanabe H&lt;/searchLink&gt;; 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.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Ko+MSH%22&quot;&gt;Ko MSH&lt;/searchLink&gt;; Department of Systems Medicine, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Ieda+M%22&quot;&gt;Ieda M&lt;/searchLink&gt;; Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Fukunaga+K%22&quot;&gt;Fukunaga K&lt;/searchLink&gt;; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Ishii+M%22&quot;&gt;Ishii M&lt;/searchLink&gt;; 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.
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– Name: Abstract
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  Data: 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.&lt;br /&gt; (Copyright &#169; 2025 The Authors. Published by Elsevier Inc. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
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  Data: 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.
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  Data: &lt;i&gt;Keywords: &lt;/i&gt;Alveolar epithelial cells; Cell therapy; Direct reprogramming; Influenza; Surfactant protein (SP)–C
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        StartPage: 152384
    Subjects:
      – SubjectFull: Fibroblasts cytology
        Type: general
      – SubjectFull: Fibroblasts metabolism
        Type: general
      – SubjectFull: Alveolar Epithelial Cells metabolism
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      – SubjectFull: Lung pathology
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      – SubjectFull: Lung virology
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      – SubjectFull: Orthomyxoviridae Infections virology
        Type: general
      – SubjectFull: Orthomyxoviridae Infections pathology
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      – SubjectFull: Orthomyxoviridae Infections therapy
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      – SubjectFull: Acute Lung Injury virology
        Type: general
      – SubjectFull: Acute Lung Injury therapy
        Type: general
      – SubjectFull: Acute Lung Injury pathology
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      – SubjectFull: Cellular Reprogramming
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      – TitleFull: Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice.
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      – PersonEntity:
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      – PersonEntity:
          Name:
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            NameFull: Okamori S
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          Name:
            NameFull: Seki M
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          Dates:
            – D: 08
              M: 09
              Text: 2025 Sep 08
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-electronic
              Value: 1090-2104
          Numbering:
            – Type: volume
              Value: 778
          Titles:
            – TitleFull: Biochemical and biophysical research communications
              Type: main
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