Journal article

Authors list: Vazquez-Armendariz, Ana Ivonne; Heiner, Monika; El Agha, Elie; Salwig, Isabelle; Hoek, Andreas; Hessler, Marie Christin; Shalashova, Irina; Shrestha, Amit; Carraro, Gianni; Mengel, Jan Philip; Günther, Andreas; Morty, Rory Edward; Vadasz, Istvan; Schwemmle, Martin; Kummer, Wolfgang; Hain, Torsten; Goesmann, Alexander; Bellusci, Saverio; Seeger, Werner; Braun, Thomas; Herold, Susanne

Publication year: 2020

Journal: The EMBO Journal

Volume number: 39

Issue number: 21

ISSN: 0261-4189

eISSN: 1460-2075

Open access status: Hybrid

DOI Link: https://doi.org/10.15252/embj.2019103476

Publisher: EMBO Press

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.

Harvard Citation style: Vazquez-Armendariz, A., Heiner, M., El Agha, E., Salwig, I., Hoek, A., Hessler, M., et al. (2020) Multilineage murine stem cells generate complex organoids to model distal lung development and disease, The EMBO Journal, 39(21), Article e103476. https://doi.org/10.15252/embj.2019103476

APA Citation style: Vazquez-Armendariz, A., Heiner, M., El Agha, E., Salwig, I., Hoek, A., Hessler, M., Shalashova, I., Shrestha, A., Carraro, G., Mengel, J., Günther, A., Morty, R., Vadasz, I., Schwemmle, M., Kummer, W., Hain, T., Goesmann, A., Bellusci, S., Seeger, W., ...Herold, S. (2020). Multilineage murine stem cells generate complex organoids to model distal lung development and disease. The EMBO Journal. 39(21), Article e103476. https://doi.org/10.15252/embj.2019103476