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Nat. Commun., 09 April 2025 | https://doi.org/10.1038/s41467-025-58450-w
Generation of induced alveolar assembloids with functional alveolar-like macrophages
Ji Su Kang1,2,7, Youngsun Lee3,7, Youngsun Lee1,2,7, Dayeon Gil3,7, Min Jung Kim3, Connor Wood4, Vincent Delorme4, Jeong Mi Lee1,2, Kyong-Cheol Ko1, Jung-Hyun Kim3,5,6 & Mi-Ok Lee1,2
1Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
2KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
3Division of Intractable Diseases Research, Department of Chronic Diseases Convergence Research, Korea National Institute of Health, Cheongju, South Korea.
4Tuberculosis Research Laboratory, Discovery Biology, Institute Pasteur Korea, Seongnam 13488, Republic of Korea.
5College of Pharmacy, Ajou University, Suwon 16499, Korea.
6Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Republic of Korea.
7These authors contributed equally: Ji Su Kang, Youngsun Lee, Youngsun Lee, Dayeon Gil.
Corresponding authors
Correspondence to Jung-Hyun Kim or Mi-Ok Lee.
1Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
2KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
3Division of Intractable Diseases Research, Department of Chronic Diseases Convergence Research, Korea National Institute of Health, Cheongju, South Korea.
4Tuberculosis Research Laboratory, Discovery Biology, Institute Pasteur Korea, Seongnam 13488, Republic of Korea.
5College of Pharmacy, Ajou University, Suwon 16499, Korea.
6Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Republic of Korea.
7These authors contributed equally: Ji Su Kang, Youngsun Lee, Youngsun Lee, Dayeon Gil.
Corresponding authors
Correspondence to Jung-Hyun Kim or Mi-Ok Lee.
Abstract
Within the human lung, interactions between alveolar epithelial cells and resident macrophages shape lung development and function in both health and disease. To study these processes, we develop a co-culture system combining human pluripotent stem cell-derived alveolar epithelial organoids and induced macrophages to create a functional environment, termed induced alveolar assembloids. Using single-cell RNA sequencing and functional analyses, we identify alveolar type 2-like cells producing GM-CSF, which supports macrophage tissue adaptation, and macrophage-like cells that secrete interleukin-1β and interleukin-6, express surfactant metabolism genes, and demonstrate core immune functions. In response to alveolar epithelial injury, macrophage-like cells efficiently eliminate damaged cells and absorb oxidized lipids. Exposure to bacterial components or infection with Mycobacterium tuberculosis reveals that these assembloids replicate key aspects of human respiratory defense. These findings highlight the potential of induced alveolar assembloids as a platform to investigate human lung development, immunity, and disease.
논문정보
- Research article
- 2025년 04월 (BRIC 등록일 2025-04-10)
- 국내 연구진
- 생명과학 > 세포생물학
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