The Hippo transducer TAZ interacts with the SWI/SNF complex to regulate breast epithelial lineage commitment

Area of Science:

• Cell Biology
• Developmental Biology
• Signaling Pathways

Background:

• Lineage-committed cells show plasticity during wound healing and cancer.
• Regulation of cell plasticity is not fully understood.

Purpose of the Study:

• Identify transcription factors regulating mammary epithelial cell lineage switching.
• Investigate the role of Hippo pathway transducer WWTR1/TAZ in mammary gland development and cell identity.

Main Methods:

• Screened transcription factors for lineage switching ability.
• Utilized forced expression and depletion of TAZ in mammary epithelial cells.
• Examined TAZ activity in human and mouse mammary tissues.
• Investigated TAZ interaction with the SWI/SNF complex.

Main Results:

• WWTR1/TAZ was identified as a key regulator of mammary epithelial cell lineage.
• Forced TAZ expression in luminal cells induced basal characteristics; TAZ depletion in basal cells caused luminal differentiation.
• TAZ is active in basal cells and essential for their maintenance during homeostasis.
• Loss of TAZ impaired mammary gland development, causing population imbalance and branching defects.
• TAZ interacts with the SWI/SNF complex to modulate lineage-specific gene expression.

Conclusions:

• WWTR1/TAZ plays a critical role in determining mammary cell lineage identity.
• Hippo signaling, via TAZ, regulates cell fate through chromatin remodeling.
• Findings reveal a novel mechanism for lineage determination in the mammary gland.