{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lim K"],"funding":["Ministry of Education","Cancer Research UK","Biogen","Medical Research Council","Allen Institute","National Research Foundation of Korea","Royal Society","Wellcome Trust","University of Cambridge"],"pagination":["20-37.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618456"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(1)"],"pubmed_abstract":["Variation in lung alveolar development is strongly linked to disease susceptibility. However, underlying cellular and molecular mechanisms are difficult to study in humans. We have identified an alveolar-fated epithelial progenitor in human fetal lungs, which we grow as self-organizing organoids that model key aspects of cell lineage commitment. Using this system, we have functionally validated cell-cell interactions in the developing human alveolar niche, showing that Wnt signaling from differentiating fibroblasts promotes alveolar-type-2 cell identity, whereas myofibroblasts secrete the Wnt inhibitor, NOTUM, providing spatial patterning. We identify a Wnt-NKX2.1 axis controlling alveolar differentiation. Moreover, we show that differential binding of NKX2.1 coordinates alveolar maturatio"],"journal":["Cell stem cell"],"pubmed_title":["Organoid modeling of human fetal lung alveolar development reveals mechanisms of cell fate patterning and neonatal respiratory disease."],"pmcid":["PMC7618456"],"funding_grant_id":["206194","103792","109146","MR/S035907/1","MR/P009581/1","103792/Z/14/Z","109146/Z/15/Z","WT206194","203144","MR/R006237/1","203144/Z/16/Z","225221","2018R1A6A3A03012122","WT211276/Z/18/Z","C6946/A24843"],"pubmed_authors":["Pett JP","Meyer KB","Brand AH","Sun D","Lim K","Marioni JC","Tang W","Donovan APA","Rawlins EL","Teichmann SA","He P"],"additional_accession":[]},"is_claimable":false,"name":"Organoid modeling of human fetal lung alveolar development reveals mechanisms of cell fate patterning and neonatal respiratory disease.","description":"Variation in lung alveolar development is strongly linked to disease susceptibility. However, underlying cellular and molecular mechanisms are difficult to study in humans. We have identified an alveolar-fated epithelial progenitor in human fetal lungs, which we grow as self-organizing organoids that model key aspects of cell lineage commitment. Using this system, we have functionally validated cell-cell interactions in the developing human alveolar niche, showing that Wnt signaling from differentiating fibroblasts promotes alveolar-type-2 cell identity, whereas myofibroblasts secrete the Wnt inhibitor, NOTUM, providing spatial patterning. We identify a Wnt-NKX2.1 axis controlling alveolar differentiation. Moreover, we show that differential binding of NKX2.1 coordinates alveolar maturatio","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-26T11:07:46.62Z","creation":"2026-05-24T03:12:08.705Z"},"accession":"S-EPMC7618456","cross_references":{"pubmed":["36493780"],"doi":["10.1016/j.stem.2022.11.013"]}}