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Updated: Feb 5, 2026
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Blastomere Explants to Test for Cell Fate Commitment During Embryonic Development
Published on: January 26, 2013
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BRD4 promotes endodermal cell fate during mammalian lung development.
Hongbo Wen1,2,3,4, Derek C Liberti1,2,3,4, Prashant Chandrasekaran1,2,3,4
1Department of Pediatrics, Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, and.
JCI Insight
|February 3, 2026
Summary
Bromodomain Containing Protein 4 (BRD4) is crucial for mammalian lung development, orchestrating early organogenesis and regulating cell fate. Its absence disrupts lung morphogenesis and airway cell specification, highlighting its multifunctional role.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Lung development requires precise regulation of cell differentiation, signaling pathways, and morphogenesis.
- Epigenetic and transcriptional regulators are essential for directing cell fate during organogenesis.
Purpose of the Study:
- To investigate the role of Bromodomain Containing Protein 4 (BRD4) in mammalian lung development and cell fate determination.
- To elucidate the specific functions of BRD4 in lung morphogenesis and cell specification.
Main Methods:
- Genetic mouse models with endodermal and temporal BRD4 deletion.
- Human embryonic stem cell (hESC)-derived lung organoid models.
- Tissue explants and single-cell transcriptomic analysis.
Main Results:
- BRD4 deletion in lung endoderm impaired epithelial-mesenchymal crosstalk, disrupting lung patterning and branching.
- Temporal BRD4 deletion caused stage-specific defects in airway and alveolar epithelial cell specification.
- BRD4 promoted lung endodermal differentiation into airway lineages in hESC-derived organoids.
Conclusions:
- BRD4 is essential for mammalian lung morphogenesis and cell fate.
- BRD4 plays distinct roles in early lung organogenesis and cell specification.
- BRD4 has a multifunctional and evolutionarily conserved role in lung development.
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