Single-cell chromatin accessibility profiling reveals a self-renewing muscle satellite cell state

Area of Science:

• Stem cell biology
• Skeletal muscle regeneration
• Epigenetics

Background:

• Tissue-resident stem cells require a balance between self-renewal and differentiation for regeneration.
• Muscle satellite cells (MuSCs) are quiescent in skeletal muscle but activate, proliferate, and differentiate for regeneration.
• Identifying self-renewing MuSCs is crucial for understanding and enhancing muscle repair.

Purpose of the Study:

• To elucidate the self-renewal versus differentiation trajectories of MuSCs during in vivo regeneration.
• To identify unique markers and molecular mechanisms governing self-renewing MuSCs.

Main Methods:

• Single-cell chromatin accessibility analysis in vivo.
• Purification and transplantation of identified self-renewing MuSCs.
• Genetic analysis of SMAD4 and downstream gene function in MuSC self-renewal.

Main Results:

• Revealed distinct self-renewal and differentiation trajectories for MuSCs during regeneration.
• Identified Betaglycan as a unique marker for self-renewing MuSCs.
• Demonstrated that SMAD4 and its downstream genes are essential for MuSC self-renewal by inhibiting differentiation.

Conclusions:

• Unveiled the molecular identity and mechanisms of self-renewing MuSCs.
• Betaglycan serves as a marker for functional self-renewing MuSCs.
• Provides a resource for studying muscle regeneration and developing regenerative therapies.