摘要：SummaryMetabolism is vital to cellular function and tissue homeostasis during human lung development.In utero, embryonic pluripotent stem cells undergo endodermal differentiation toward a lung progenitor cell fate that can be mimickedin vitrousing induced human pluripotent stem cells (hiPSCs) to study genetic mutations. To identify differences between wild-type and surfactant protein B (SFTPB)-deficient cell lines during endoderm specification toward lung, we used an untargeted metabolomics approach to evaluate the developmental changes in metabolites. We found that the metabolites most enriched during the differentiation from pluripotent stem cell to lung progenitor cell, regardless of cell line, were sphingomyelins and phosphatidylcholines, two important lipid classes in lung development. TheSFTPBmutation had no metabolic impact on early endodermal lung development. The identified metabolite signatures during lung progenitor cell differentiation may be utilized as biomarkers for normal embryonic lung development.Graphical abstractDisplay OmittedHighlights•Largest metabolic changes occurred from pluripotent cells to definitive endoderm•Differentiation to lung progenitor cell increased fatty acid metabolism•Differentiation to lung progenitor cell decreased urea cycle/aspartate metabolism•No significant differences between metabolites in wild type vs SPB mutant endodermCell biology; Stem cells research; Metabolomics
