Bulk RNA sequencing of human pediatric lung cell populations reveals unique transcriptomic signature associated with postnatal pulmonary development

Gautam Bandyopadhyay1, Matthew G. Jehrio1, Cameron Baker1, Soumyaroop Bhattacharya1, Ravi Misra1, Heidi L. Huyck1, ChinYi Chu1, Jason R. Myers1, John Ashton1, Steven Polter1, Matthew Cochran1, Timothy Bushnell1, Jennifer Dutra1, Philip J. Katzman1, Gail H. Deutsch, Thomas J. Mariani1, Gloria Pryhuber1
1University of Rochester Medical Center, *Corresponding author
Description Postnatal lung development results in an increasingly functional organ prepared for gas exchange and pathogenic challenges. It is achieved through cellular differentiation and migration. Changes in the tissue architecture during this development process are well-documented and increasing cellular diversity associated with it are reported in recent years. Despite recent progress, transcriptomic and molecular pathways associated with human postnatal lung development are yet to be fully understood. In this study, we investigated gene expression patterns associated with healthy pediatric lung development in four major enriched cell populations (epithelial, endothelial, and nonendothelial mesenchymal cells, along with lung leukocytes) from 1-day-old to 8-yr-old organ donors with no known lung disease. For analysis, we considered the donors in four age groups [less than 30 days old neonates, 30 days to < 1 yr old infants, toddlers (1 to < 2 yr), and children 2 yr and older] and assessed differentially expressed genes (DEG). We found increasing age-associated transcriptional changes in all four major cell types in pediatric lung. Transition from neonate to infant stage showed highest number of DEG compared with the number of DEG found during infant to toddler- or toddler to older children-transitions. Profiles of differential gene expression and further pathway enrichment analyses indicate functional epithelial cell maturation and increased capability of antigen presentation and chemokine-mediated communication. Our study provides a comprehensive reference of gene expression patterns during healthy pediatric lung development that will be useful in identifying and understanding aberrant gene expression patterns associated with early life respiratory diseases. NEW & NOTEWORTHY This study presents postnatal transcriptomic changes in major cell populations in human lung, namely endothelial, epithelial, mesenchymal cells, and leukocytes. Although human postnatal lung development continues through early adulthood, our results demonstrate that greatest transcriptional changes occur in first few months of life during neonate to infant transition. These early transcriptional changes in lung parenchyma are particularly notable for functional maturation and activation of alveolar type II cell genes.
Dataset ID LMEX0000003691
Assay Type RNA-seq
Organism Human
Stages Neonate | Infant | Child | Adult
Sample Count 151
Sample Prep Lmdata:sample_type_sorted_cells
FileDescriptionSize
Cell Sorting ResultsCell sorting results157.6 KB
Data Table (Normalized Counts)Normalized counts output from deSeq2 (CPM)26.8 MB
Data Table (Raw Counts)Raw counts generated using STAR aligner on gencode 28. See report in RNA Extraction for further details in data processing5.8 MB
RNA QCRNA QC (Bioanalyzer results including RIN and concentration)20.8 KB
RNA-seq QCRNA-seq QC (GRC post read processing results)5.8 MB
Sample MetadataSample Metadata24.8 KB
LungMAP IDAlt IDSpeciesSexRaceAgeAge GroupGA at BirthCGAWeightWeight PercentileCause of DeathType of Death
LMSP0000000131D008Homo sapiensFemaleWhite20 monthsChild12.25 kg86Trauma - Auto AccidentDBD (after brain death)
LMSP0000000134D011Homo sapiensFemaleWhite20 monthsChild40 weeks10.89 kg53Anoxic/Hypoxic Brain Injury - DrowningDBD (after brain death)
LMSP0000000141D018Homo sapiensFemaleWhite3 yearsChild15 kg73Anoxic/Hypoxic Brain Injury - DrowningDBD (after brain death)
LMSP0000000142D019Homo sapiensMaleWhite1 daysNeonate37 weeks, 3 days37.43 weeksCongenital Anomaly - BrainDCD (circulatory death)
LMSP0000000145D022Homo sapiensMaleOther2 yearsChild11.79 kg12Trauma - Isolated Head TraumaDBD (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)
LMSP0000000159D038Homo sapiensFemaleUnknown or Not Reported1 daysNeonate39 weeks, 3 days39.57 weeks2.27 kg1.2Congenital Anomaly - BrainDCD (circulatory death)
LMSP0000000162D041Homo sapiensMaleWhite6 daysNeonate38 weeks, 3 days39.14 weeks3.24 kg33Anoxic/Hypoxic Brain Injury - OtherDCD (circulatory death)
LMSP0000000164D043Homo sapiensMaleWhite21 monthsChild9.8 kg6.2Trauma - Isolated Head TraumaDBD (after brain death)
LMSP0000000165D044Homo sapiensMaleWhite6 daysNeonate40 weeks, 3 days41.57 weeks3.63 kg56Anoxic/Hypoxic Brain Injury - Neonatal HIEDCD (circulatory death)
LMSP0000000177D056Homo sapiensMaleWhite5 yearsChild22.23 kg77Trauma - Auto AccidentDBD (after brain death)
LMSP0000000184D063Homo sapiensMaleAfrican American16 monthsChild11.2 kg65Trauma - OtherDBD (after brain death)
LMSP0000000192D071Homo sapiensMaleWhite24 yearsAdult90 kgToxin or Drug ExposureDCD (circulatory death)
LMSP0000000196D075Homo sapiensMaleWhite4 monthsInfant6.8 kg31Anoxic/Hypoxic Brain Injury - SIDSDBD (after brain death)
LMSP0000000213D092Homo sapiensFemaleAfrican American2 monthsInfant40 weeks, 3 days49 weeks5 kg42Anoxic/Hypoxic Brain Injury - SIDSDBD (after brain death)
LMSP0000001012D105Homo sapiensFemaleWhite6 monthsInfant40 weeks8.7 kg92Trauma - Auto AccidentDBD (after brain death)
LMSP0000001017D110Homo sapiensMaleUnknown or Not Reported3 monthsInfant40 weeks, 3 days58 weeks7.71 kg79Stroke or Intracranial HemorrhageDBD (after brain death)
LMSP0000001020D113Homo sapiensMaleAfrican American5 monthsInfant40 weeks66.14 weeks8.3 kg65Trauma - OtherDBD (after brain death)
LMSP0000001023D116Homo sapiensFemaleAfrican American40 yearsAdult88 kgAnoxic/Hypoxic Brain Injury - OtherDBD (after brain death)
LMSP0000001026D119Homo sapiensMaleWhite13 monthsChild40 weeks11.7 kg91Infection - MeningitisDBD (after brain death)
LMSP0000001040D133Homo sapiensMaleAfrican American11 monthsInfant40 weeks, 3 days89.57 weeks10.43 kg81Trauma - Fall from HeightDBD (after brain death)
LMSP0000001041D134Homo sapiensFemaleWhite8 yearsChild27.5 kg58Trauma - Auto AccidentDBD (after brain death)
LMSP0000001043D136Homo sapiensMaleWhite16 monthsChild8.7 kg3Anoxic/Hypoxic Brain Injury - OtherDBD (after brain death)
LMSP0000001050D143Homo sapiensMaleAfrican American3 monthsInfant6.35 kg49Anoxic/Hypoxic Brain Injury - SIDSDBD (after brain death)

26 of this study's 26 samples were also assayed by 448 other LungMAP studies, across 9 modalities. Click any node to list those studies.