Proteomic Analysis of Human Lung Development

Charles Ansong1, Gloria Pryhuber2, Geremy Clair1
1Pacific Northwest National Laboratory, 2University of Rochester Medical Center, *Corresponding author
Description 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.
Dataset ID LMEX0000004395
Assay Type Proteomics
Organism Human
Stages Neonate | Infant | Child
Sample Count 11
Sample Prep Lmdata:sample_type_biopsy
External databases Proteome Xchange: PXD020798
FileDescriptionSize
Clair et al. (2022) Supplement29.1 MB
LungMAP IDAlt IDSpeciesSexRaceAgeAge GroupGA at BirthCGAWeightWeight PercentileCause of DeathType of Death
LMSP0000000128D004Homo sapiensMaleWhite5 daysNeonate41 weeks41.71 weeks3.63 kg63Anoxic/Hypoxic Brain Injury - Neonatal HIEDBD (after brain death)
LMSP0000000129D005Homo sapiensMaleWhite1 daysNeonate39 weeks, 6 days39.86 weeks2.87 kg17Congenital Anomaly - BrainDCD (circulatory death)
LMSP0000000034D007Homo sapiensMaleAfrican American4 yearsChild15.42 kg21Trauma - Isolated Head TraumaDBD (after brain death)
LMSP0000000135D012Homo sapiensMaleWhite2 yearsChild19.5 kg100Anoxic/Hypoxic Brain Injury - DrowningDBD (after brain death)
LMSP0000000142D019Homo sapiensMaleWhite1 daysNeonate37 weeks, 3 days37.43 weeksCongenital Anomaly - BrainDCD (circulatory death)
LMSP0000000143D020Homo sapiensMaleOther24 daysNeonate41 weeks, 1 days44.57 weeks4.08 kg39Anoxic/Hypoxic Brain Injury - SIDSDBD (after brain death)
LMSP0000000035D024Homo sapiensMaleOther4 monthsInfant8.62 kg94Trauma - Auto AccidentDBD (after brain death)
LMSP0000000152D031Homo sapiensMaleWhite7 monthsInfant40 weeks7.26 kg7.4Anoxic/Hypoxic Brain Injury - SIDSDBD (after brain death)
LMSP0000000157D036Homo sapiensMaleWhite8 yearsChild34 kg89Trauma - Isolated Head TraumaDBD (after brain death)
LMSP0000000168D047Homo sapiensMaleWhite12 daysNeonate36 weeks37.86 weeks3.3 kg67Stroke or Intracranial HemorrhageDBD (after brain death)
LMSP0000000173D052Homo sapiensMaleAfrican American13 monthsChild9.5 kg33Trauma - Auto AccidentDBD (after brain death)

9 of this study's 11 samples were also assayed by 145 other LungMAP studies, across 10 modalities. Click any node to list those studies. The other 2 appear in no other study and are not drawn.