Abstract
Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylphosphatidylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murine lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6–8 week mice (adult) identified 924 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. This multi-omic view provides a unique resource and deeper insight into normal pulmonary development.
Highlights
Immature lung is the primary cause of respiratory distress syndrome (RDS)
The post-natal day 7 (PND7) and PND14 time-points span peak stages of alveologenesis[14], during which the alveoli that are critical for the air/gas exchange function of the lung form
924 unique lipid species covering 3 lipid categories and 21 lipid subclasses (Fig. 1) were confidently identified based on their MS/MS fragmentation patterns, representing one of the largest lipidome datasets reported to date
Summary
Immature lung is the primary cause of RDS. variations in species and distributions of lipids in the lungs are implicated in the outcomes of cystic fibrosis[8], lung cancer[9], and asthma[10]. Our LC-MS/MS-based lipidomics analysis resulted in identification of 924 lipid species across 21 lipid subclasses, providing a deep and comprehensive view of the lung lipidome during normal development We complemented these untargeted lipidomics measurements with additional untargeted proteomics (8289 total proteins, Table S2) and metabolomics (178 total metabolites, Table S3) analyses from the same samples to provide a more comprehensive picture of lipid metabolism during normal lung development. These types of multi-omics analyses have been shown to enhance our understanding of biological systems[12,15]. Our multi-omic measurement approach offers unique insights into mammalian respiratory system development
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