Datasets and R scripts related to the manuscript "In vitro generation of human pluripotent stem cell derived lung organoids"
In vitro generation of human pluripotent stem cell derived lung organoids
Briana R. Dye2, David R. Hill1, Michael A.H. Ferguson1, Melinda S. Nagy1, Rachel Dyal1, James M. Wells4,5, Christopher N. Mayhew4, Roy Nattiv6, Ophir D. Klein6,7,8, Eric S. White1, Gail H. Deutsch9, Jason R. Spence1,2,3,#
1Department of Internal Medicine, 2Department of Cell and Developmental Biology, 3Center for Organogenesis, University of Michigan Medical School, Ann Arbor, MI 48109 4Division of Developmental Biology, 5Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 6Institute for Human Genetics and Department of Pediatrics; 7Program in Craniofacial and Mesenchymal Biology; 8Center for Craniofacial Anomalies, University of California San Francisco, San Franciso, CA, USA, 94143 9Department of Laboratories, Seattle Children's Hospital and University of Washington, Seattle, Washington, USA 98105
Author for Correspondence: spencejr@umich.edu
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 the human fetal lung based on global transcriptional profiles, suggesting that HLOs are an excellent model to study human lung development, maturation and disease.