Metabolomic profiling of human pluripotent stem cell differentiation into lung progenitors
Sandra L. Leibel,
Irene Tseu,
Anson Zhou,
Andrew Hodges,
Jun Yin,
Claudia Bilodeau,
Olivia Goltsis,
Martin Post
Affiliations
Sandra L. Leibel
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92037, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Corresponding author
Irene Tseu
Translational Medicine Program, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada
Anson Zhou
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
Andrew Hodges
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
Jun Yin
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
Claudia Bilodeau
Translational Medicine Program, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada
Olivia Goltsis
Translational Medicine Program, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada
Martin Post
Translational Medicine Program, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada
Summary: Metabolism 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 mimicked in vitro using 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. The SFTPB mutation 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.
