In vitro generation of human pluripotent stem cell derived lung organoids
Briana R Dye,
David R Hill,
Michael AH Ferguson,
Yu-Hwai Tsai,
Melinda S Nagy,
Rachel Dyal,
James M Wells,
Christopher N Mayhew,
Roy Nattiv,
Ophir D Klein,
Eric S White,
Gail H Deutsch,
Jason R Spence
Affiliations
Briana R Dye
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States
David R Hill
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States
Michael AH Ferguson
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States
Yu-Hwai Tsai
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States
Melinda S Nagy
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States
Rachel Dyal
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States
James M Wells
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States; Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
Christopher N Mayhew
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
Roy Nattiv
Institute for Human Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, United States
Ophir D Klein
Institute for Human Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, United States; Program in Craniofacial and Mesenchymal Biology, University of California, San Francisco, San Francisco, United States; Center for Craniofacial Anomalies, University of California, San Francisco, San Francisco, United States
Eric S White
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States
Gail H Deutsch
Department of Laboratories, Seattle Children's Hospital and University of Washington, Seattle, United States
Jason R Spence
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; Center for Organogenesis, University of Michigan Medical School, Ann Arbor, 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.
