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Single-cell transcriptomics reveals lasting changes in the lung cellular landscape into adulthood after neonatal
Alejandro Scaffa1, Hongwei Yao1, Nathalie Oulhen1
1Department of Molecular Biology, Cell Biology & Biochemistry, Division of Biology and Medicine, Brown University, Providence, RI, United States.
Redox Biology
|August 21, 2021
Summary
Neonatal exposure to high oxygen levels, a treatment for premature infants, can cause lasting lung damage. This early-life hyperoxia alters lung cell composition, leading to adult pulmonary dysfunction.
Area of Science:
- Pulmonary Medicine
- Neonatology
- Cellular Biology
Background:
- Ventilatory support, including supplemental oxygen, is crucial for premature infants but can impair lung development, leading to bronchopulmonary dysplasia (BPD).
- While many BPD survivors are weaned off oxygen early, they may experience persistent adult lung injury and dysfunction.
- Early-life hyperoxia's long-term effects on lung cellular composition and adult function remain incompletely understood.
Purpose of the Study:
- To investigate if early-life hyperoxia exposure alters the lung cellular landscape in later life.
- To determine if these alterations predict long-term lung injury and dysfunction.
- To identify specific cell type changes associated with neonatal hyperoxia and their potential link to human BPD.
Main Methods:
- Utilized single-cell RNA sequencing to map lung cell subpopulations in neonatal mice.
- Analyzed lung cells at postnatal day 7 and postnatal day 60 following a 3-day exposure to 95% oxygen as neonates.
- Interrogated over 10,000 cells, identifying 45 clusters within 32 distinct cell states.
Main Results:
- Neonatal hyperoxia induced persistent compositional changes in all five type II cell states by postnatal day 60, with unique signatures and functions affected.
- Similar alterations in type II cell state signatures were observed in premature infants requiring mechanical ventilation.
- Pathological examination revealed alveolar simplification in adult mice following neonatal hyperoxic exposure.
Conclusions:
- Neonatal hyperoxia significantly alters the lung cellular landscape in adult mice, indicating a programming of adult lung dysfunction.
- These findings highlight the long-term consequences of early-life respiratory support on lung development and function.
- The study identifies specific cellular changes that may serve as biomarkers for predicting long-term lung injury in BPD survivors.

