Systems biology of lung development and regeneration: current knowledge and recommendations for future research

The lung begins as a simple outpouching of the foregut and develops by stages into a highly complex organ, the proper function of which is essential to life for terrestrial mammals. Interruption of normal lung development can result in death or chronic disease. Conversely, repair after lung injury, as well as many acquired diseases, involves recapitulation, often aberrant, of developmental pathways. The principal paradigms in lung development are branching morphogenesis and alveolar septation, but others, such as vasculogenesis, are critical. These are partially understood at the level of cellular differentiation and molecular signaling, but a true systems biology analysis of lung development and lung repair/regeneration, including bioinformatics analysis and integration of data from unbiased and complementary '-omics' level studies, is still lacking. The past decade has seen increasing numbers of genomic, proteomic, metabolomics, and epigenomic studies of lung development and lung remodeling. In many cases, these studies have confirmed the importance of pathways uncovered painstakingly through single-molecule approaches, but they have also uncovered novel and unexpected pathways and new paradigms such as noncoding RNA. Future studies will need to combine data from multiple repositories and apply novel mathematical and computational models in order to establish a systems-level understanding of this remarkable organ.