Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells
Abstract Direct reprogramming is a breakthrough technology that can alter the fate of cells without the passage of stem cells. However, direct reprogramming of somatic cells into pulmonary alveolar epithelial cells has not yet been achieved. Here, we report the direct reprogramming of mouse tail tip...
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Nature Portfolio
2025-06-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-025-00411-4 |
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| author | Atsuho Morita Makoto Ishii Takanori Asakura Masaya Yotsukura Ahmed E. Hegab Tatsuya Kusumoto Ho Namkoong Takunori Ogawa Yuhki Nakatake Mayumi Oda Fumitake Saito Hirofumi Kamata Junko Hamamoto Satoshi Okamori Toshiki Ebisudani Hiroyuki Yasuda Shinya Sugimoto Yuta Kuze Masahide Seki Yutaka Suzuki Naoki Hasegawa Hisao Asamura Hideo Watanabe Minoru Ko Toshiro Sato Masaki Ieda Koichi Fukunaga |
| author_facet | Atsuho Morita Makoto Ishii Takanori Asakura Masaya Yotsukura Ahmed E. Hegab Tatsuya Kusumoto Ho Namkoong Takunori Ogawa Yuhki Nakatake Mayumi Oda Fumitake Saito Hirofumi Kamata Junko Hamamoto Satoshi Okamori Toshiki Ebisudani Hiroyuki Yasuda Shinya Sugimoto Yuta Kuze Masahide Seki Yutaka Suzuki Naoki Hasegawa Hisao Asamura Hideo Watanabe Minoru Ko Toshiro Sato Masaki Ieda Koichi Fukunaga |
| author_sort | Atsuho Morita |
| collection | DOAJ |
| description | Abstract Direct reprogramming is a breakthrough technology that can alter the fate of cells without the passage of stem cells. However, direct reprogramming of somatic cells into pulmonary alveolar epithelial cells has not yet been achieved. Here, we report the direct reprogramming of mouse tail tips and embryonic fibroblasts into induced pulmonary alveolar epithelial-like cells (iPULs) using four transcription factor-coding genes (Nkx2-1, Foxa1, Foxa2, and Gata6) and three-dimensional culture. The iPULs showed lamellar body-like structures and displayed key properties of pulmonary alveolar epithelial cells. Although the potential for iPULs to morphologically differentiate into alveolar epithelial type 1 cells was limited in vitro, the intratracheal administration of iPULs in a bleomycin-induced mouse model of pulmonary fibrosis led to their integration into the alveolar surface, where they formed both alveolar epithelial type 1 and type 2-like cells. Thus, reprogrammed fibroblasts may represent a new source of pulmonary alveolar epithelial cells for regenerative medicine. |
| format | Article |
| id | doaj-art-62fbebb399d249148335f6d666f7c148 |
| institution | Kabale University |
| issn | 2057-3995 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj-art-62fbebb399d249148335f6d666f7c1482025-08-20T03:24:22ZengNature Portfolionpj Regenerative Medicine2057-39952025-06-0110111610.1038/s41536-025-00411-4Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cellsAtsuho Morita0Makoto Ishii1Takanori Asakura2Masaya Yotsukura3Ahmed E. Hegab4Tatsuya Kusumoto5Ho Namkoong6Takunori Ogawa7Yuhki Nakatake8Mayumi Oda9Fumitake Saito10Hirofumi Kamata11Junko Hamamoto12Satoshi Okamori13Toshiki Ebisudani14Hiroyuki Yasuda15Shinya Sugimoto16Yuta Kuze17Masahide Seki18Yutaka Suzuki19Naoki Hasegawa20Hisao Asamura21Hideo Watanabe22Minoru Ko23Toshiro Sato24Masaki Ieda25Koichi Fukunaga26Division of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Thoracic Surgery, Department of Surgery, Keio University School of MedicineMedical Education Center, International University of Health and WelfareDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDepartment of Infectious Diseases, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDepartment of Systems Medicine, Keio University School of MedicineDepartment of Integrated Medicine and Biochemistry, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of MedicineDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoDepartment of Infectious Diseases, Keio University School of MedicineDivision of Thoracic Surgery, Department of Surgery, Keio University School of MedicineDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Icahn School of Medicine at Mount SinaiDepartment of Infectious Diseases, Keio University School of MedicineDepartment of Integrated Medicine and Biochemistry, Keio University School of MedicineDepartment of Cardiology, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineAbstract Direct reprogramming is a breakthrough technology that can alter the fate of cells without the passage of stem cells. However, direct reprogramming of somatic cells into pulmonary alveolar epithelial cells has not yet been achieved. Here, we report the direct reprogramming of mouse tail tips and embryonic fibroblasts into induced pulmonary alveolar epithelial-like cells (iPULs) using four transcription factor-coding genes (Nkx2-1, Foxa1, Foxa2, and Gata6) and three-dimensional culture. The iPULs showed lamellar body-like structures and displayed key properties of pulmonary alveolar epithelial cells. Although the potential for iPULs to morphologically differentiate into alveolar epithelial type 1 cells was limited in vitro, the intratracheal administration of iPULs in a bleomycin-induced mouse model of pulmonary fibrosis led to their integration into the alveolar surface, where they formed both alveolar epithelial type 1 and type 2-like cells. Thus, reprogrammed fibroblasts may represent a new source of pulmonary alveolar epithelial cells for regenerative medicine.https://doi.org/10.1038/s41536-025-00411-4 |
| spellingShingle | Atsuho Morita Makoto Ishii Takanori Asakura Masaya Yotsukura Ahmed E. Hegab Tatsuya Kusumoto Ho Namkoong Takunori Ogawa Yuhki Nakatake Mayumi Oda Fumitake Saito Hirofumi Kamata Junko Hamamoto Satoshi Okamori Toshiki Ebisudani Hiroyuki Yasuda Shinya Sugimoto Yuta Kuze Masahide Seki Yutaka Suzuki Naoki Hasegawa Hisao Asamura Hideo Watanabe Minoru Ko Toshiro Sato Masaki Ieda Koichi Fukunaga Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells npj Regenerative Medicine |
| title | Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells |
| title_full | Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells |
| title_fullStr | Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells |
| title_full_unstemmed | Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells |
| title_short | Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells |
| title_sort | direct reprogramming of mouse fibroblasts into self renewable alveolar epithelial like cells |
| url | https://doi.org/10.1038/s41536-025-00411-4 |
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