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Elife. 2015 Mar 24;4. doi: 10.7554/eLife.05098.

In vitro generation of human pluripotent stem cell derived lung organoids.

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Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
Institute for Human Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, United States.
Department of Laboratories, Seattle Children's Hospital and University of Washington, Seattle, United States.


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.


developmental biology; endoderm; foregut; human; lung; organoids; pluripotent stem cells; spheroid; stem cells

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