Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells.
Autor: | Hawkins FJ; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA., Suzuki S; Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA., Beermann ML; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA., Barillà C; Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA., Wang R; Pulmonary and Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA., Villacorta-Martin C; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA., Berical A; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA., Jean JC; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA., Le Suer J; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA., Matte T; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA., Simone-Roach C; Pulmonary and Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA., Tang Y; Boston Children's Hospital Stem Cell Program, Boston, MA 02115, USA., Schlaeger TM; Boston Children's Hospital Stem Cell Program, Boston, MA 02115, USA; Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA., Crane AM; Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA., Matthias N; Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA., Huang SXL; Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA., Randell SH; Marsico Lung Institute and Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Wu J; Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Spence JR; Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI 48109, USA., Carraro G; Department of Medicine, Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Stripp BR; Department of Medicine, Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Rab A; Emory University School of Medicine, Atlanta, GA 30322, USA., Sorsher EJ; Emory University School of Medicine, Atlanta, GA 30322, USA., Horani A; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Brody SL; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Davis BR; Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA. Electronic address: brian.r.davis@uth.tmc.edu., Kotton DN; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA. Electronic address: dkotton@bu.edu. |
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Jazyk: | angličtina |
Zdroj: | Cell stem cell [Cell Stem Cell] 2021 Jan 07; Vol. 28 (1), pp. 79-95.e8. Date of Electronic Publication: 2020 Oct 23. |
DOI: | 10.1016/j.stem.2020.09.017 |
Abstrakt: | The derivation of tissue-specific stem cells from human induced pluripotent stem cells (iPSCs) would have broad reaching implications for regenerative medicine. Here, we report the directed differentiation of human iPSCs into airway basal cells ("iBCs"), a population resembling the stem cell of the airway epithelium. Using a dual fluorescent reporter system (NKX2-1 GFP ;TP63 tdTomato ), we track and purify these cells as they first emerge as developmentally immature NKX2-1 GFP+ lung progenitors and subsequently augment a TP63 program during proximal airway epithelial patterning. In response to primary basal cell medium, NKX2-1 GFP+ /TP63 tdTomato+ cells display the molecular and functional phenotype of airway basal cells, including the capacity to self-renew or undergo multi-lineage differentiation in vitro and in tracheal xenografts in vivo. iBCs and their differentiated progeny model perturbations that characterize acquired and genetic airway diseases, including the mucus metaplasia of asthma, chloride channel dysfunction of cystic fibrosis, and ciliary defects of primary ciliary dyskinesia. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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