Fibrosis: Lessons from OMICS analyses of the human lung

In recent decades there has been a significant shift in our understanding of idiopathic pulmonary fibrosis (IPF), a progressive and lethal disorder. While initially much of the mechanistic understanding was derived from hypotheses generated from animal models of disease, in recent decades new insights derived from humans with IPF have taken precedence. This is mainly because of the establishment of large collections of IPF lung tissues and patient cohorts, and the emergence of high throughput profiling technologies collectively termed 'omics' technologies based on their shared suffix. In this review we describe impacts of 'omics' analyses of human IPF samples on our understanding of the disease. In particular, we discuss the results of genomics and transcriptomics studies, as well as proteomics, epigenomics and metabolomics. We then describe how these findings can be integrated in a modified paradigm of human idiopathic pulmonary fibrosis, that introduces the 'hallmarks of aging' as a central theme in the IPF lung. This allows resolution of all the disparate cellular and molecular features in IPF, from the central role of epithelial cells, through the dramatic phenotypic alterations observed in fibroblasts and the numerous aberrations that inflammatory cells exhibit. We end with reiterating a call for renewed efforts to collect and analyze carefully characterized human tissues, in ways that would facilitate implementation of novel technologies for high resolution single cell omics profiling.