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. (LMEX0000004395)
Geremy Clair (PNNL) | Charles Ansong (PNNL) | Gloria Pryhuber (HTC/URMC)
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Chart Type
Transformation
Primary Grouping
Secondary Grouping
LungMAP ID Alt ID Species Sex Race Age Age Group GA at Birth CGA Weight Weight Percentile Cause of Death Type of Death Health Status
LMSP0000000128 D004 Homo sapiens Male White 5 days Neonate 41 weeks, 0 days 41.86 weeks 3.63 kg 61 Anoxic/Hypoxic Brain Injury DBD (after brain death) No known lung disease
LMSP0000000129 D005 Homo sapiens Male White 1 day Neonate 39 weeks, 6 days 39.86 weeks 2.87 kg 17 Congenital Anomaly DCD (circulatory death) No known lung disease
LMSP0000000034 D007 Homo sapiens Male African American 4 years Child 15.42 kg 17 Trauma DBD (after brain death) No known lung disease
LMSP0000000135 D012 Homo sapiens Male White 2 years Child 19.5 kg 100 Anoxic/Hypoxic Brain Injury DBD (after brain death) No known lung disease
LMSP0000000142 D019 Homo sapiens Male White 1 day Neonate 37 weeks, 3 days 37.43 weeks kg 0 Congenital Anomaly DCD (circulatory death) No known lung disease
LMSP0000000143 D020 Homo sapiens Male Other 24 days Neonate 41 weeks, 1 days 44.57 weeks 4.08 kg 39 Anoxic/Hypoxic Brain Injury DBD (after brain death) No known lung disease
LMSP0000000035 D024 Homo sapiens Male Other 4 months Infant 8.62 kg 94 Trauma DBD (after brain death) No known lung disease
LMSP0000000152 D031 Homo sapiens Male White 7 months Infant 7.26 kg 8.2 Anoxic/Hypoxic Brain Injury DBD (after brain death) No known lung disease
LMSP0000000157 D036 Homo sapiens Male White 8 years Child 34 kg 89 Trauma DBD (after brain death) No known lung disease
LMSP0000000168 D047 Homo sapiens Male White 12 days Neonate 36 weeks, 0 days 37.71 weeks 3.3 kg 67 Other DBD (after brain death) No known lung disease
LMSP0000000173 D052 Homo sapiens Male African American 13 months Child 9.5 kg 32 Trauma DBD (after brain death) No known lung disease