title: In vitro generation of human pluripotent stem cell derived lung organoids.
abstract: 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.
authors: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
authors: Briana R
authors: BR
authors: Dye
authors: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
authors: David R
authors: DR
authors: Hill
authors: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
authors: Michael A H
authors: MA
authors: Ferguson
authors: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
authors: Yu-Hwai
authors: YH
authors: Tsai
authors: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
authors: Melinda S
authors: MS
authors: Nagy
authors: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
authors: Rachel
authors: R
authors: Dyal
authors: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
authors: James M
authors: JM
authors: Wells
authors: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
authors: Christopher N
authors: CN
authors: Mayhew
authors: Institute for Human Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, United States.
authors: Roy
authors: R
authors: Nattiv
authors: Institute for Human Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, United States.
authors: Ophir D
authors: OD
authors: Klein
authors: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
authors: Eric S
authors: ES
authors: White
authors: Department of Laboratories, Seattle Children's Hospital and University of Washington, Seattle, United States.
authors: Gail H
authors: GH
authors: Deutsch
authors: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
authors: Jason R
authors: JR
authors: Spence
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D038081:Organogenesis; D009940:Organoids / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods
keywords: developmental biology; endoderm; foregut; human; lung; organoids; pluripotent stem cells; spheroid; stem cells