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Human alveolar progenitors generate dual lineage bronchioalveolar organoids

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Item Type:Article
Title:Human alveolar progenitors generate dual lineage bronchioalveolar organoids
Creators Name:Hoffmann, K. and Obermayer, B. and Hönzke, K. and Fatykhova, D. and Demir, Z. and Löwa, A. and Teixeira-Alves, L.G. and Wyler, E. and Lopez-Rodriguez, E. and Mieth, M. and Baumgardt, M. and Hoppe, J. and Firsching, T.C. and Tönnies, M. and Bauer, T.T. and Eggeling, S. and Tran, H.L. and Schneider, P. and Neudecker, J. and Rückert, J.C. and Gruber, A.D. and Ochs, M. and Landthaler, M. and Beule, D. and Suttorp, N. and Hippenstiel, S. and Hocke, A.C. and Kessler, M.
Abstract: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.
Keywords:Cell Differentiation, Glycogen Synthase Kinase 3 beta, Lung, Organoids, Wnt Signaling Pathway
Source:Communications Biology
ISSN:2399-3642
Publisher:Springer Nature
Volume:5
Number:1
Page Range:875
Date:25 August 2022
Official Publication:https://doi.org/10.1038/s42003-022-03828-5
PubMed:View item in PubMed

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