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Tytuł:
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Progenitor identification and SARS-CoV-2 infection in human distal lung organoids.
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Autorzy:
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Salahudeen AA; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Division of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, USA.
Choi SS; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Rustagi A; Division of Infectious Disease and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Zhu J; Stanford University School of Engineering, Department of Electrical Engineering, Stanford, CA, USA.
van Unen V; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
de la O SM; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Flynn RA; Stanford ChEM-H, Stanford University, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA.
Margalef-Català M; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Santos AJM; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Ju J; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Batish A; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Usui T; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Zheng GXY; 10x Genomics, Pleasanton, CA, USA.
Edwards CE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Wagar LE; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
Luca V; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
Anchang B; Division of Biomedical Data Science, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Nagendran M; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Nguyen K; Division of Gastroenterology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Hart DJ; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Terry JM; 10x Genomics, Pleasanton, CA, USA.
Belgrader P; 10x Genomics, Pleasanton, CA, USA.
Ziraldo SB; 10x Genomics, Pleasanton, CA, USA.
Mikkelsen TS; 10x Genomics, Pleasanton, CA, USA.
Harbury PB; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.
Glenn JS; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.; Division of Gastroenterology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Garcia KC; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
Davis MM; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sabatti C; Division of Biomedical Data Science, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Amieva MR; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Blish CA; Division of Infectious Disease and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. .; Chan Zuckerberg Biohub, San Francisco, CA, USA. .
Desai TJ; Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. .
Kuo CJ; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. .
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Źródło:
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Nature [Nature] 2020 Dec; Vol. 588 (7839), pp. 670-675. Date of Electronic Publication: 2020 Nov 25.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
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MeSH Terms:
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Models, Biological*
Tissue Culture Techniques*
COVID-19/*virology
Lung/*cytology
Organoids/*cytology
Organoids/*virology
SARS-CoV-2/*physiology
Alveolar Epithelial Cells/cytology ; Alveolar Epithelial Cells/metabolism ; Alveolar Epithelial Cells/virology ; COVID-19/metabolism ; COVID-19/pathology ; Cell Differentiation ; Cell Division ; Clone Cells/cytology ; Clone Cells/metabolism ; Clone Cells/virology ; Humans ; In Vitro Techniques ; Influenza A Virus, H1N1 Subtype/growth & development ; Influenza A Virus, H1N1 Subtype/physiology ; Integrin alpha6/analysis ; Integrin beta4/analysis ; Keratin-5/analysis ; Organoids/metabolism ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/pathology ; Pneumonia, Viral/virology ; SARS-CoV-2/growth & development ; Single-Cell Analysis ; TWEAK Receptor/analysis
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References:
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Hogan, B. & Tata, P. R. Cellular organization and biology of the respiratory system. Nat. Cell Biol. https://doi.org/10.1038/s41556-019-0357-7 (2019).
Rawlins, E. L. et al. The role of Scgb1a1 intestinal stem-cell self-renewal. Nature 545, 238–242 (2017). (PMID: 28467820564147110.1038/nature22313)
Van der Velden, J. L., Bertoncello, I. & McQualter, J. L. LysoTracker is a marker of differentiated alveolar type II cells. Respir. Res. 14, 123 (2013). (PMID: 24215602384066010.1186/1465-9921-14-123)
Chang, J. et al. Gpr124 is essential for blood-brain barrier integrity in central nervous system disease. Nat. Med. 23, 450–460 (2017). (PMID: 28288111555938510.1038/nm.4309)
Nagendran, M., Riordan, D. P., Harbury, P. B. & Desai, T. J. Automated cell-type classification in intact tissues by single-cell molecular profiling. eLife 7, e30510 (2018). (PMID: 29319504580284310.7554/eLife.30510)
Neal, J. T. et al. Organoid modeling of the tumor immune microenvironment. Cell 175, 1972–1988.e16 (2018). (PMID: 30550791665668710.1016/j.cell.2018.11.021)
Dobbs, L. G., Williams, M. C. & Brandt, A. E. Changes in biochemical characteristics and pattern of lectin binding of alveolar type II cells with time in culture. Biochim. Biophys. Acta 846, 155–166 (1985). (PMID: 383941810.1016/0167-4889(85)90121-1)
Van Lidth de Jeude, J. F., Vermeulen, J. L., Montenegro-Miranda, P. S., Van den Brink, G. R. & Heijmans, J. A protocol for lentiviral transduction and downstream analysis of intestinal organoids. J. Vis. Exp. 98, e52531 (2015).
Manicassamy, B. et al. Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus. Proc. Natl Acad. Sci. USA 107, 11531–11536 (2010). (PMID: 20534532289512310.1073/pnas.0914994107)
Karaca, G. et al. TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice. PLoS ONE 9, e83987 (2014). (PMID: 24416188388697310.1371/journal.pone.0083987)
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Grant Information:
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T32 GM007365 United States GM NIGMS NIH HHS; R01 AI157155 United States AI NIAID NIH HHS; DK11572802 United States NH NIH HHS; U24 DK085532 United States DK NIDDK NIH HHS; U01 DE025188 United States DE NIDCR NIH HHS; UH3 CA255135 United States CA NCI NIH HHS; U01 DK085532 United States DK NIDDK NIH HHS; UG3 HL145623 United States HL NHLBI NIH HHS; T32 AI007502-23 United States NH NIH HHS; United Kingdom WT_ Wellcome Trust; T32 AI007502 United States AI NIAID NIH HHS; R01 HL142549 United States HL NHLBI NIH HHS; T32 GM007365-44 United States NH NIH HHS; U01 CA176299 United States CA NCI NIH HHS; R56 AI111460 United States AI NIAID NIH HHS; 5R01HL14254902 United States NH NIH HHS; United States HHMI Howard Hughes Medical Institute; U19 AI057229 United States AI NIAID NIH HHS; K08 DE027730 United States DE NIDCR NIH HHS; U01 DK085527 United States DK NIDDK NIH HHS; U01 CA217851 United States CA NCI NIH HHS; U19 AI116484 United States AI NIAID NIH HHS
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Substance Nomenclature:
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0 (ITGA6 protein, human)
0 (ITGB4 protein, human)
0 (Integrin alpha6)
0 (Integrin beta4)
0 (KRT5 protein, human)
0 (Keratin-5)
0 (TNFRSF12A protein, human)
0 (TWEAK Receptor)
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Entry Date(s):
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Date Created: 20201125 Date Completed: 20210106 Latest Revision: 20240409
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Update Code:
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20240409
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PubMed Central ID:
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PMC8003326
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DOI:
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10.1038/s41586-020-3014-1
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PMID:
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33238290
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The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate the investigation of pathologies such as interstitial lung disease, cancer and coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we describe the development of a long-term feeder-free, chemically defined culture system for distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) or KRT5 + basal cells. AT2 organoids were able to differentiate into AT1 cells, and basal cell organoids developed lumens lined with differentiated club and ciliated cells. Single-cell analysis of KRT5 + cells in basal organoids revealed a distinct population of ITGA6 + ITGB4 + mitotic cells, whose offspring further segregated into a TNFRSF12A hi subfraction that comprised about ten per cent of KRT5 + basal cells. This subpopulation formed clusters within terminal bronchioles and exhibited enriched clonogenic organoid growth activity. We created distal lung organoids with apical-out polarity to present ACE2 on the exposed external surface, facilitating infection of AT2 and basal cultures with SARS-CoV-2 and identifying club cells as a target population. This long-term, feeder-free culture of human distal lung organoids, coupled with single-cell analysis, identifies functional heterogeneity among basal cells and establishes a facile in vitro organoid model of human distal lung infections, including COVID-19-associated pneumonia.
Update of: bioRxiv. 2020 Jul 27;:. (PMID: 32743583)
