Publikationsdatenbank

Human alveolar progenitors generate dual lineage bronchioalveolar organoids (2022)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Hoffmann, Karen

Obermayer, Benedikt

Hönzke, Katja

Fatykhova, Diana

Demir, Zeynep

Löwa, Anna

Alves, Luiz Gustavo Teixeira

Wyler, Emanuel

Lopez-Rodriguez, Elena

Mieth, Maren

Baumgardt, Morris

Hoppe, Judith (WE 12)

Firsching, Theresa C. (WE 12)

Tönnies, Mario

Bauer, Torsten T.

Eggeling, Stephan

Tran, Hong-Linh

Schneider, Paul

Neudecker, Jens

Rückert, Jens C.

Gruber, Achim D. (WE 12)

Ochs, Matthias

Landthaler, Markus

Beule, Dieter

Suttorp, Norbert

Hippenstiel, Stefan

Hocke, Andreas C.

Kessler, Mirjana

Quelle

Communications biology

Bandzählung: 5

Heftzählung: 1

Seiten: Article number: 875

ISSN: 2399-3642

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s42003-022-03828-5

DOI: 10.1038/s42003-022-03828-5

Pubmed: 36008580

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Mechanisms of epithelial renewal in the alveolar compartment remain incompletely understood. To this end, we aimed to characterize alveolar progenitors. Single-cell RNA-sequencing (scRNA-seq) analysis of the HTII-280+/EpCAM+ population from adult human lung revealed subclusters enriched for adult stem cell signature (ASCS) genes. We found that alveolar progenitors in organoid culture in vitro show phenotypic lineage plasticity as they can yield alveolar or bronchial cell-type progeny. The direction of the differentiation is dependent on the presence of the GSK-3β inhibitor, CHIR99021. By RNA-seq profiling of GSK-3β knockdown organoids we identified additional candidate target genes of the inhibitor, among others FOXM1 and EGF. This gives evidence of Wnt pathway independent regulatory mechanisms of alveolar specification. Following influenza A virus (IAV) infection organoids showed a similar response as lung tissue explants which confirms their suitability for studies of sequelae of pathogen-host interaction.