Snail/Slug binding interactions with YAP/TAZ control skeletal stem cell self-renewal and differentiation

Area of Science:

• Stem Cell Biology
• Molecular Biology
• Skeletal Biology

Background:

• Skeletal stem/stromal cells (SSCs) are crucial for bone development, homeostasis, and repair.
• The precise mechanisms governing SSC self-renewal and osteogenic differentiation are not fully understood.

Purpose of the Study:

• To elucidate the regulatory mechanisms controlling skeletal stem cell behavior, focusing on bone formation.
• To identify key transcription factors and signaling pathways involved in SSC self-renewal and osteoblastogenesis.

Main Methods:

• Utilized knockout mouse models targeting Snail and Slug transcription factors, individually and in combination.
• Investigated the interaction of Snail/Slug with YAP/TAZ co-activators and the Hippo signaling pathway.
• Analyzed downstream targets of the Snail/Slug-YAP/TAZ axis, including YAP/TAZ/TEAD and Runx2.

Main Results:

• Snail and Slug cooperatively regulate SSC self-renewal, osteoblastogenesis, and bone formation.
• Snail/Slug form complexes with YAP and TAZ, inhibiting Hippo pathway-dependent YAP/TAZ regulation.
• The Snail/Slug-YAP/TAZ axis activates downstream targets essential for SSC homeostasis and osteogenesis.

Conclusions:

• A novel regulatory axis involving Snail, Slug, YAP, and TAZ controls skeletal stem cell function.
• SSCs utilize Snail/Slug-YAP/TAZ complexes to manage stem cell behavior and bone formation.
• This finding provides critical insights into the molecular control of skeletal stem cell fate and bone regeneration.