Transcript profile distinguishes variability in human myogenic progenitor cell expansion capacity

Area of Science:

• Skeletal muscle biology
• Cellular regenerative processes
• Molecular genetics

Background:

• Primary human muscle progenitor cells (hMPCs) are crucial for studying skeletal muscle biology and regeneration.
• Expansion capacity of hMPCs exhibits variability unrelated to donor disease status, age, or sex.

Purpose of the Study:

• To identify transcript profiles differentiating hMPC cultures with higher expansion capacity.
• To elucidate the underlying biological mechanisms driving these transcriptome differences.

Main Methods:

• hMPCs were sorted (CD56+/CD29+) and clustered into FAST and SLOW groups based on growth parameters using K-means analysis.
• RNA sequencing was performed on hMPCs during their expansion phase.
• Differential gene expression analysis and pathway enrichment were conducted to compare FAST and SLOW groups.

Main Results:

• FAST hMPCs demonstrated significantly enhanced expansion capacity, including reduced doubling time and increased saturation density.
• Transcriptome analysis revealed 2,205 differentially expressed genes between FAST and SLOW hMPCs.
• Enrichment analysis indicated that FAST hMPCs exhibit promoted cell cycle, reduced apoptosis and senescence, and enhanced DNA replication.

Conclusions:

• Variations in hMPC expansion capacity are intrinsic and not dictated by donor age or sex.
• Specific intrinsic molecular mechanisms promoting the cell cycle are key drivers of enhanced hMPC expansion.
• Identified genes like RABL6, IRGM1, AREG, FOXM1, CDKN1A, and Rb are potential regulators of hMPC expansion capacity.