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<p>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 (<i>Nkx2-1</i>, <i>Foxa1</i>, <i>Foxa2</i>, and <i>Gata6</i>) 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.</p>

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Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月23日

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  • 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

摘要

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.