bioRxiv
Cambridge Institute for Medical Research, Cambridge, CB2 0XY, UK.
Published: September 2023
Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases including interstitial lung disease (ILD), in which some inherited forms result from mislocalisation of surfactant protein C (SFTPC) variants. Disease modelling and dissection of mechanisms remains challenging due to complexities in deriving and maintaining AT2 cells Here, we describe the development of expandable adult AT2-like organoids derived from human fetal lung which are phenotypically stable, can differentiate into AT1-like cells and are genetically manipulable. We use these organoids to test key effectors of SFTPC maturation identified in a forward genetic screen including the E3 ligase ITCH, demonstrating that their depletion phenocopies the pathological SFTPC redistribution seen for the SFTPC-I73T variant. In summary, we demonstrate the development of a novel alveolar organoid model and use it to identify effectors of SFTPC maturation necessary for AT2 health.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491189 | PMC |
http://dx.doi.org/10.1101/2023.08.30.555522 | DOI Listing |
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School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; National Institute of Science and Technology for Detection, Toxicological Evaluation and Removal of Micropollutants and Radioactive Substances (INCT-DATREM). Electronic address:
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