In vitro generation of human pluripotent stem cell derived lung organoids

By Briana R. Dye, David R. Hill, Michael A. J. Ferguson, Y. Tsai, Melinda S. Nagy, R. Dyal, James M. Wells, C. Mayhew, Roy Nattiv, O. Klein and 3 more. eLife, 2015

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Recent breakthroughs in 3-dimensional (3D) organoid cultures for many organ systems have led to new physiologically complex in vitro models to study human development and disease. Here, we report the step-wise differentiation of human pluripotent stem cells (hPSCs) (embryonic and induced) into lung organoids. By manipulating developmental signaling pathways hPSCs generate ventral-anterior foregut spheroids, which are then expanded into human lung organoids (HLOs). HLOs consist of epithelial and mesenchymal compartments of the lung, organized with structural features similar to the native lung. HLOs possess upper airway-like epithelium with basal cells and immature ciliated cells surrounded by smooth muscle and myofibroblasts as well as an alveolar-like domain with appropriate cell types. Using RNA-sequencing, we show that HLOs are remarkably similar to human fetal lung based on global transcriptional profiles, suggesting that HLOs are an excellent model to study human lung development, maturation and disease. DOI: http://dx.doi.org/10.7554/eLife.05098.001

Subfields: Molecular Biology, Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/05d66b37a5b2987184cc271272a2f82ea9adbdc3

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Citations in the corpus

Long‐term expanding human airway organoids for disease modeling (2019, positive): “Spence and colleagues (Dye et al , 2015) followed a modified trajectory to generate mature lung organoids, containing basal, ciliated, and club cells.”
Modeling Development and Disease with Organoids. (2016, background): “Spence and colleagues (Dye et al., 2015) similarly started from Activin-treated human PSCs but then followed a slightly different trajectory.”
Biology-inspired Microphysiological System Approaches to Solve the Prediction Dilemma of Substance Testing (2016, positive): “…et al., 2007; Leist et al., 2008) Pluripotent stem cells of the origin described above have been used for the de novo assembly of human gastric (McCracken et al., 2011), cerebral (Lancaster et al., 2013), kidney (Xia et al., 2014) and lung organoids (Dye et al., 2015) in static culture systems.”