Proteomic Analysis of Human Lung Development
Gérémy Clair, Lisa Bramer, Ravi Misra, Matthew McGraw, Soumyaroop Bhattacharya, Joseph A. Kitzmiller, Song Feng, Vincent Danna, Gautam Bandyopadhyay, Harsh Bhotika, Heidie Huyck, Gail Deutsch, Thomas J. Mariani, James P. Carson, Jeffrey A. Whitsett, Gloria Pryhuber, Joshua Adkins, Charles Ansong
Abstract
Abstract Rationale The current understanding of human lung development derives mostly from animal studies. Although transcript-level studies have analyzed human donor tissue to identify genes expressed during normal human lung development, protein-level analysis that would enable the generation of new hypotheses on the processes involved in pulmonary development are lacking. Objectives To define the temporal dynamic of protein expression during human lung development. Methods We performed proteomics analysis of human lungs at 10 distinct times from birth to 8 years to identify the molecular networks mediating postnatal lung maturation. Measurements and Main Results We identified 8,938 proteins providing a comprehensive view of the developing human lung proteome. The analysis of the data supports the existence of distinct molecular substages of alveolar development and predicted the age of independent human lung samples, and extensive remodeling of the lung proteome occurred during postnatal development. Evidence of post-transcriptional control was identified in early postnatal development. An extensive extracellular matrix remodeling was supported by changes in the proteome during alveologenesis. The concept of maturation of the immune system as an inherent part of normal lung development was substantiated by flow cytometry and transcriptomics. Conclusions This study provides the first in-depth characterization of the human lung proteome during development, providing a unique proteomic resource freely accessible at Lungmap.net. The data support the extensive remodeling of the lung proteome during development, the existence of molecular substages of alveologenesis, and evidence of post-transcriptional control in early postnatal development.