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Title: Time-resolved Proteome Profiling of Normal Lung Development

Abstract

The biochemical networks mediating normal lung development remain unclear with important implications for ameliorating morbidity and mortality in premature infants. Here we perform integrative proteomics and metabolomics analyses of murine lungs from embryonic to early adult ages to characterize the molecular networks mediating normal lung development. Multi-omics analysis identified 8,932 proteins and 158 polar metabolites providing a deep and comprehensive view of the lung proteome and metabolome during normal development. Analysis of the proteomics data revealed ten discrete expression modules driving lung development and the underlying regulatory and signaling network modulating these expression modules. Of interest our data suggest the action of protein ubiquitination in regulating lung development extends beyond the pseudoglandular stage previously described. Combined analysis of the proteomics and metabolomics supported the notion of increased cell proliferation earlier in lung development. Additionally, comparison of the proteomics data with a recent transcriptome analysis revealed biological processes under post-transcriptional control during lung development. Our study provides a unique resource for understanding normal lung development, and potentially avenues for developing strategies to address disrupted development.

Authors:
 [1]; ORCiD logo [1];  [1];  [2]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1];  [1]; ORCiD logo [1];  [3]; ORCiD logo [1];  [1];  [2];  [1]
  1. BATTELLE (PACIFIC NW LAB)
  2. Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center
  3. University of Texas at Austin
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1558266
Report Number(s):
PNNL-SA-127218
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
American Journal of Physiology-Lung Cellular and Molecular Physiology
Additional Journal Information:
Journal Volume: 315; Journal Issue: 1
Country of Publication:
United States
Language:
English
Subject:
computational network analysis, lung development, morphogenesis, proteomics

Citation Formats

Moghieb, Ahmed M., Clair, Geremy CD, Mitchell, Hugh D., Kitzmiller, Joseph, Zink, Erika M., Kim, Young-Mo, Petyuk, Vladislav A., Shukla, Anil K., Moore, Ronald J., Metz, Thomas O., Carson, James P., McDermott, Jason E., Corley, Richard A., Whitsett, Jeff, and Ansong, Charles K. Time-resolved Proteome Profiling of Normal Lung Development. United States: N. p., 2018. Web. doi:10.1152/ajplung.00316.2017.
Moghieb, Ahmed M., Clair, Geremy CD, Mitchell, Hugh D., Kitzmiller, Joseph, Zink, Erika M., Kim, Young-Mo, Petyuk, Vladislav A., Shukla, Anil K., Moore, Ronald J., Metz, Thomas O., Carson, James P., McDermott, Jason E., Corley, Richard A., Whitsett, Jeff, & Ansong, Charles K. Time-resolved Proteome Profiling of Normal Lung Development. United States. doi:10.1152/ajplung.00316.2017.
Moghieb, Ahmed M., Clair, Geremy CD, Mitchell, Hugh D., Kitzmiller, Joseph, Zink, Erika M., Kim, Young-Mo, Petyuk, Vladislav A., Shukla, Anil K., Moore, Ronald J., Metz, Thomas O., Carson, James P., McDermott, Jason E., Corley, Richard A., Whitsett, Jeff, and Ansong, Charles K. Sun . "Time-resolved Proteome Profiling of Normal Lung Development". United States. doi:10.1152/ajplung.00316.2017.
@article{osti_1558266,
title = {Time-resolved Proteome Profiling of Normal Lung Development},
author = {Moghieb, Ahmed M. and Clair, Geremy CD and Mitchell, Hugh D. and Kitzmiller, Joseph and Zink, Erika M. and Kim, Young-Mo and Petyuk, Vladislav A. and Shukla, Anil K. and Moore, Ronald J. and Metz, Thomas O. and Carson, James P. and McDermott, Jason E. and Corley, Richard A. and Whitsett, Jeff and Ansong, Charles K.},
abstractNote = {The biochemical networks mediating normal lung development remain unclear with important implications for ameliorating morbidity and mortality in premature infants. Here we perform integrative proteomics and metabolomics analyses of murine lungs from embryonic to early adult ages to characterize the molecular networks mediating normal lung development. Multi-omics analysis identified 8,932 proteins and 158 polar metabolites providing a deep and comprehensive view of the lung proteome and metabolome during normal development. Analysis of the proteomics data revealed ten discrete expression modules driving lung development and the underlying regulatory and signaling network modulating these expression modules. Of interest our data suggest the action of protein ubiquitination in regulating lung development extends beyond the pseudoglandular stage previously described. Combined analysis of the proteomics and metabolomics supported the notion of increased cell proliferation earlier in lung development. Additionally, comparison of the proteomics data with a recent transcriptome analysis revealed biological processes under post-transcriptional control during lung development. Our study provides a unique resource for understanding normal lung development, and potentially avenues for developing strategies to address disrupted development.},
doi = {10.1152/ajplung.00316.2017},
journal = {American Journal of Physiology-Lung Cellular and Molecular Physiology},
number = 1,
volume = 315,
place = {United States},
year = {2018},
month = {7}
}

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