tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Masaya Yotsukura[SUP] 2 [/SUP], Takanori Asakura[SUP] 3 [/SUP], Ho Namkoong[SUP] 4 [/SUP], Takunori Ogawa[SUP] 5 [/SUP], Ahmed E Hegab[SUP] 6 [/SUP], Yuhki Nakatake[SUP] 7 [/SUP], Mayumi Oda[SUP] 8 [/SUP], Fumitake Saito[SUP] 3 [/SUP], Hirofumi Kamata[SUP] 9 [/SUP], Junko Hamamoto[SUP] 3 [/SUP], Satoshi Okamori[SUP] 3 [/SUP], Masahide Seki[SUP] 10 [/SUP], Yutaka Suzuki[SUP] 10 [/SUP], Naoki Hasegawa[SUP] 4 [/SUP], Hisao Asamura[SUP] 11 [/SUP], Hideo Watanabe[SUP] 12 [/SUP], Minoru S H Ko[SUP] 7 [/SUP], Masaki Ieda[SUP] 13 [/SUP], Koichi Fukunaga[SUP] 3 [/SUP], Makoto Ishii[SUP] 14 [/SUP]
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[SUP] 1 [/SUP], Masaya Yotsukura[SUP] 2 [/SUP], Takanori Asakura[SUP] 3 [/SUP], Ho Namkoong[SUP] 4 [/SUP], Takunori Ogawa[SUP] 5 [/SUP], Ahmed E Hegab[SUP] 6 [/SUP], Yuhki Nakatake[SUP] 7 [/SUP], Mayumi Oda[SUP] 8 [/SUP], Fumitake Saito[SUP] 3 [/SUP], Hirofumi Kamata[SUP] 9 [/SUP], Junko Hamamoto[SUP] 3 [/SUP], Satoshi Okamori[SUP] 3 [/SUP], Masahide Seki[SUP] 10 [/SUP], Yutaka Suzuki[SUP] 10 [/SUP], Naoki Hasegawa[SUP] 4 [/SUP], Hisao Asamura[SUP] 11 [/SUP], Hideo Watanabe[SUP] 12 [/SUP], Minoru S H Ko[SUP] 7 [/SUP], Masaki Ieda[SUP] 13 [/SUP], Koichi Fukunaga[SUP] 3 [/SUP], Makoto Ishii[SUP] 14 [/SUP]
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.