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

Plos One
|August 24, 2012
PubMed

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.

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Transcription01:10

Transcription

Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription01:17

Transcription

Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in correctly synthesizing messenger RNA (mRNA). Transcriptional regulation is responsible for the differentiation of different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...