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Cell fate specification during respiratory development requires ARID1A-containing canonical BAF complex activity
Hyunwook Lee1,2,3,4,5, Abigail Jaquish6,7, Sharlene Fernandes1,2
1Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Nature Communications
|April 21, 2026
Summary
The BAF complex is crucial for mammalian lung development, controlling gene regulation for lung formation and cell differentiation. Its loss impairs distal patterning and AT1 cell development, highlighting its essential role.
Area of Science:
- Developmental biology
- Epigenetics
- Molecular biology
Background:
- Mammalian lung development involves complex gene regulation for formation, patterning, and cell specification.
- While transcriptional and signaling pathways are known, epigenetic regulators remain less understood.
Purpose of the Study:
- To investigate the role of the BAF (BRG1-associated factor) complex in mammalian lung epithelial development.
- To identify the specific functions and downstream effects of BAF complex activity in lung organogenesis.
Main Methods:
- Utilized genetic deletion models (complete loss and ARID1A deletion) in mammalian systems.
- Performed epigenomic analyses to assess enhancer activation.
- Employed embryonic murine lung organoid models with BMP4 treatment.
Main Results:
- Complete BAF complex loss results in failed lung formation.
- ARID1A deletion disrupts distal patterning, reduces alveolar type 1 (AT1) cell differentiation, and promotes a proliferative state via YAP/WNT activation.
- Epigenomic analysis revealed widespread failure in cell type-specific enhancer activation.
- BMP4 treatment rescued distal differentiation in organoids, while YAP/WNT signaling necessitates functional BAF complex.
Conclusions:
- The BAF complex is essential for mammalian lung epithelial development, regulating key processes like patterning and differentiation.
- BAF complex activity is required for proper response to signaling pathways, including BMP, YAP, and WNT.
- These findings reveal differential pathway specificities and highlight the BAF complex as a critical epigenetic regulator in lung organogenesis.
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