Generation of Alveolar Epithelial Spheroids via Isolated Progenitor Cells from Human Pluripotent Stem Cells
Shimpei Gotoh,Isao Ito,Tadao Nagasaki,Yuki Yamamoto,Satoshi Konishi,Yohei Korogi,Hisako Matsumoto,Shigeo Muro,Toyohiro Hirai,Michinori Funato,Shin-Ichi Mae,Taro Toyoda,Aiko Sato-Otsubo,Seishi Ogawa,Kenji Osafune,Michiaki Mishima +15 more
TL;DR: 3D coculture differentiation of CPM+ cells formed spheroids with lamellar-body-like structures and an increased expression of surfactant proteins compared with 2D differentiation to aid human pulmonary disease modeling and regenerative medicine.
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Abstract: No methods for isolating induced alveolar epithelial progenitor cells (AEPCs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have been reported. Based on a study of the stepwise induction of alveolarepithelial cells (AECs), we identified carboxypeptidase M (CPM) as a surface marker of NKX2-1 + ‘‘ventralized’’ anterior foregut endoderm cells (VAFECs) in vitro and in fetalhumanandmurinelungs.UsingSFTPC-GFPreporterhPSCsanda3Dcoculturesystemwithfetalhumanlungfibroblasts,weshowed that CPM + cells isolated from VAFECs differentiate into AECs, demonstrating that CPM is a marker of AEPCs. Moreover, 3D coculture differentiation of CPM + cells formed spheroids with lamellar-body-like structures and an increased expression of surfactant proteins compared with 2D differentiation. Methods to induce and isolate AEPCs using CPM and consequently generate alveolar epithelial spheroids would aid human pulmonary disease modeling and regenerative medicine.
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Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells.
Anjali Jacob,Anjali Jacob,Michael Morley,Finn Hawkins,Finn Hawkins,Katherine B. McCauley,Katherine B. McCauley,J. C. Jean,J. C. Jean,Hillary B. Heins,Cheng-Lun Na,Timothy E. Weaver,Marall Vedaie,Marall Vedaie,Killian Hurley,Killian Hurley,Anne Hinds,Scott J. Russo,Seunghyi Kook,William J. Zacharias,Matthias Ochs,Katrina E. Traber,Lee J. Quinton,Ana M. Crane,Brian R. Davis,Frances V. White,Jennifer A. Wambach,Jeffrey A. Whitsett,F. Sessions Cole,Edward E. Morrisey,Susan H. Guttentag,Michael F. Beers,Darrell N. Kotton,Darrell N. Kotton +33 more
TL;DR: PSC-derived AEC2s provide a platform for disease modeling and future functional regeneration of the distal lung, and exhibit self-renewal capacity, and display additional A EC2 functional capacities.
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Efficient Derivation of Functional Human Airway Epithelium from Pluripotent Stem Cells via Temporal Regulation of Wnt Signaling.
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Generation of lung organoids from human pluripotent stem cells in vitro.
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TL;DR: Key aspects of lung repair and regeneration are discussed, including the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung Repair and regeneration.
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