Multilineage murine stem cells generate complex organoids to model distal lung development and disease
Abstract: Organoids derived from mouse and human stem cells have recently emerged as a powerful tool to study organ development and disease. We here established a three‐dimensional (3D) murine bronchioalveolar lung organoid (BALO) model that allows clonal expansion and self‐organization of FACS‐sorted bronchioalveolar stem cells (BASCs) upon co‐culture with lung‐resident mesenchymal cells. BALOs yield a highly branched 3D structure within 21 days of culture, mimicking the cellular composition of the bronchioalveolar compartment as defined by single‐cell RNA sequencing and fluorescence as well as electron microscopic phenotyping. Additionally, BALOs support engraftment and maintenance of the cellular phenotype of injected tissue‐resident macrophages. We also demonstrate that BALOs recapitulate lung developmental defects after knockdown of a critical regulatory gene, and permit modeling of viral infection. We conclude that the BALO model enables reconstruction of the epithelial–mesenchymal‐myeloid unit of the distal lung, thereby opening numerous new avenues to study lung development, infection, and regenerative processes in vitro
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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The EMBO journal. - (2020) , e103476, ISSN: 1460-2075
- Klassifikation
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Medizin, Gesundheit
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2020
- Urheber
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Vázquez Armendariz, Ana Ivonne
Heiner, Monika
Agha, Elie el
Salwig, Isabelle
Hoek, Andreas
Hessler, Marie Christin
Shalashova, Irina
Shrestha, Amit
Carraro, Gianni
Mengel, Jan Philip
Günther, Andreas
Morty, Rory E.
Vadász, István
Schwemmle, Martin
Kummer, Wolfgang
Hain, Torsten
Goesmann, Alexander
Bellusci, Saverio
Seeger, Werner
Braun, Thomas
Herold, Susanne
- DOI
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10.15252/embj.2019103476
- URN
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urn:nbn:de:bsz:25-freidok-1675878
- Rechteinformation
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 10:53 MESZ
Datenpartner
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Beteiligte
- Vázquez Armendariz, Ana Ivonne
- Heiner, Monika
- Agha, Elie el
- Salwig, Isabelle
- Hoek, Andreas
- Hessler, Marie Christin
- Shalashova, Irina
- Shrestha, Amit
- Carraro, Gianni
- Mengel, Jan Philip
- Günther, Andreas
- Morty, Rory E.
- Vadász, István
- Schwemmle, Martin
- Kummer, Wolfgang
- Hain, Torsten
- Goesmann, Alexander
- Bellusci, Saverio
- Seeger, Werner
- Braun, Thomas
- Herold, Susanne
- Universität
Entstanden
- 2020