Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm

Area of Science:

• Developmental biology
• Stem cell biology
• Gene regulation

Background:

• Tbx3 is a T-box transcription factor crucial for development, stem cells, reprogramming, and cancer.
• Loss of Tbx3 typically induces differentiation in mouse embryonic stem cells (mESCs).

Purpose of the Study:

• To investigate the role of Tbx3 in maintaining pluripotency and controlling cell fate transitions in mESCs.
• To elucidate the molecular mechanisms by which Tbx3 regulates Wnt signaling and differentiation.

Main Methods:

• Transcriptome analysis of mESCs lacking Tbx3.
• Identification of direct downstream targets of Tbx3.
• Functional studies on Tbx3's regulation of Wnt pathway members.

Main Results:

• mESCs lacking Tbx3 exist in an alternative stable pluripotent state.
• Dppa3 was identified as a direct downstream target of Tbx3.
• Tbx3 directly represses Wnt pathway components, facilitating the transition to mesoderm progenitors.
• Tbx3 fine-tunes the dual roles of Wnt signaling in maintaining pluripotency and promoting differentiation.

Conclusions:

• A novel signaling-transcription factor (TF) axis involving Tbx3 and Wnt signaling controls the exit from pluripotency towards mesoderm differentiation in mESCs.
• Tbx3 plays a critical role in maintaining naive pluripotency and regulating lineage commitment.