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Published on: April 12, 2021
Transcriptional programs controlling perinatal lung maturation
Yan Xu1, Yanhua Wang, Valérie Besnard
1The Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. yan.xu@cchmc.org
Insights
This study mapped gene expression during lung maturation in mice, identifying key regulators and pathways. Findings offer insights into enhancing lung function in preterm infants, potentially reducing Respiratory Distress Syndrome and Broncho-Pulmonary Dysplasia.
Area of Science:
- Developmental Biology
- Genomics
- Neonatology
Background:
- Preterm birth often leads to Respiratory Distress Syndrome (RDS) and Broncho-Pulmonary Dysplasia (BPD) due to immature lungs.
- Understanding the genetic and cellular programs controlling lung maturation is crucial for preventing these conditions.
Purpose of the Study:
- To elucidate mechanisms synchronizing gestational length and lung maturation.
- To identify key regulators, bioprocesses, and transcriptional networks controlling lung maturation.
Main Methods:
- Genome-wide mRNA expression time-course study in C57BL/6J and A/J mice from E15.5 to Postnatal Day 0 (PN0).
- Comprehensive bioinformatics and functional genomics analyses.
Main Results:
- Identified temporal and strain-dependent gene expression patterns during lung maturation.
- Cell adhesion, vasculature development, and lipid metabolism were key during the saccular stage.
- Innate immune responses were induced later, while cell cycle and chromatin assembly genes were repressed.
- Strain-specific differences in surfactant, innate immunity, and chromatin assembly gene expression were observed.
Conclusions:
- Systematically mapped key regulators and networks controlling lung maturation.
- Provides a basis for developing new therapeutic strategies to improve lung function in preterm infants.
Abstract:
The timing of lung maturation is controlled precisely by complex genetic and cellular programs. Lung immaturity following preterm birth frequently results in Respiratory Distress Syndrome (RDS) and Broncho-Pulmonary Dysplasia (BPD), which are leading causes of mortality and morbidity in preterm infants. Mechanisms synchronizing gestational length and lung maturation remain to be elucidated. In this study, we designed a genome-wide mRNA expression time-course study from E15.5 to Postnatal Day 0 (PN0) using lung RNAs from C57BL/6J (B6) and A/J mice that differ in gestational length by ∼30 hr (B6
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