Generation of human alveolar epithelial type I cells from pluripotent stem cells.

Autor:	Burgess CL; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Huang J; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Bawa PS; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA., Alysandratos KD; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Minakin K; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Ayers LJ; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Morley MP; Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Babu A; Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Villacorta-Martin C; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA., Yampolskaya M; Department of Physics, Boston University, Boston, MA 02215, USA., Hinds A; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Thapa BR; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Wang F; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA., Matschulat A; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Department of Biochemistry and Cell Biology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Mehta P; Department of Physics, Boston University, Boston, MA 02215, USA., Morrisey EE; Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Varelas X; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Department of Biochemistry and Cell Biology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Kotton DN; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA. Electronic address: dkotton@bu.edu.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2024 May 02; Vol. 31 (5), pp. 657-675.e8. Date of Electronic Publication: 2024 Apr 19.
DOI:	10.1016/j.stem.2024.03.017
Abstrakt:	Alveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and find that nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier producing characteristic extracellular matrix molecules and secreted ligands. Our results provide an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s. Competing Interests: Declaration of interests The authors have filed a patent application related to the generation of human alveolar epithelial type I cells from pluripotent stem cells detailed in this manuscript. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu