A Myc-driven self-reinforcing regulatory network maintains mouse embryonic stem cell identity

Area of Science:

• Stem cell biology
• Epigenetics
• Molecular signaling

Background:

• Stem cell identity relies on integrating extrinsic and intrinsic signals to maintain epigenetic states.
• Myc transcription factors are vital for stem cell self-renewal and pluripotency, but their interaction with signaling pathways and epigenetic regulators is unclear.

Purpose of the Study:

• To investigate how Myc integrates with signaling pathways and epigenetic regulators in embryonic stem cells (ESCs).
• To elucidate the role of Myc in maintaining ESC self-renewal and pluripotency.

Main Methods:

• Profiling gene expression and epigenetic patterns in ESCs with conditional Myc activity.
• Analyzing the interaction between Myc, Wnt/β-catenin signaling, and epigenetic regulators.

Main Results:

• Myc activation potentiates the Wnt/β-catenin signaling pathway, cooperating with the transcriptional network to sustain ESC self-renewal.
• Myc directly recruits PRC2 to repress Wnt antagonists, leading to enhanced autocrine Wnt/β-catenin signaling.
• This potentiation induces endogenous Myc family members, establishing a Myc-driven self-reinforcing circuit.

Conclusions:

• Myc establishes a self-propagating epigenetic memory essential for maintaining ESC self-renewal capacity.
• Myc plays a critical role in the epigenetic regulation of stem cell pluripotency and self-renewal through Wnt signaling.