Tweet
Biochem Biophys Res Commun
. 2025 Jul 17:778:152384.
doi: 10.1016/j.bbrc.2025.152384. Online ahead of print. Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice
Tatsuya Kusumoto 1 , Masaya Yotsukura 2 , Takanori Asakura 3 , Ho Namkoong 4 , Takunori Ogawa 5 , Ahmed E Hegab 6 , Yuhki Nakatake 7 , Mayumi Oda 8 , Fumitake Saito 3 , Hirofumi Kamata 9 , Junko Hamamoto 3 , Satoshi Okamori 3 , Masahide Seki 10 , Yutaka Suzuki 10 , Naoki Hasegawa 4 , Hisao Asamura 11 , Hideo Watanabe 12 , Minoru S H Ko 7 , Masaki Ieda 13 , Koichi Fukunaga 3 , Makoto Ishii 14
Affiliations
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.
Keywords: Alveolar epithelial cells; Cell therapy; Direct reprogramming; Influenza; Surfactant protein (SP)–C.
. 2025 Jul 17:778:152384.
doi: 10.1016/j.bbrc.2025.152384. Online ahead of print. Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice
Tatsuya Kusumoto 1 , Masaya Yotsukura 2 , Takanori Asakura 3 , Ho Namkoong 4 , Takunori Ogawa 5 , Ahmed E Hegab 6 , Yuhki Nakatake 7 , Mayumi Oda 8 , Fumitake Saito 3 , Hirofumi Kamata 9 , Junko Hamamoto 3 , Satoshi Okamori 3 , Masahide Seki 10 , Yutaka Suzuki 10 , Naoki Hasegawa 4 , Hisao Asamura 11 , Hideo Watanabe 12 , Minoru S H Ko 7 , Masaki Ieda 13 , Koichi Fukunaga 3 , Makoto Ishii 14
Affiliations
- PMID: 40700809
- DOI: 10.1016/j.bbrc.2025.152384
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.
Keywords: Alveolar epithelial cells; Cell therapy; Direct reprogramming; Influenza; Surfactant protein (SP)–C.