Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes

Area of Science:

• Comparative genomics
• Skeletal muscle biology
• Transcriptomics

Background:

• Skeletal muscle transcriptome profiles differ across muscle types in mice and humans.
• Identifying conserved molecular signatures between mouse and human skeletal muscle is crucial for translational research.

Purpose of the Study:

• To determine which mouse skeletal muscle group exhibits the greatest molecular similarity to human skeletal muscle.
• To assess the muscle-specificity of observed transcriptomic similarities.

Main Methods:

• Comparative analysis of orthologous whole and sub-transcriptome profiles.
• Utilized four datasets: mouse skeletal muscles (six groups, three strains), human quadriceps (biopsy), human skeletal muscles (autopsy), and human non-muscle tissues.
• Statistical comparison of transcriptome data across species and tissue types.

Main Results:

• The mouse soleus muscle demonstrated the highest molecular similarity to human skeletal muscles, irrespective of human muscle type, disease status, age, or sampling method.
• No significant molecular similarity was found between mouse skeletal muscles and human non-muscle tissues, confirming muscle specificity.
• This conserved similarity highlights the soleus as a valuable model for studying human skeletal muscle biology.

Conclusions:

• The mouse soleus muscle is a highly relevant model for human skeletal muscle research.
• Higher type I fiber content in the soleus may contribute to its molecular conservation with human skeletal muscle.
• Transcriptomic similarities are specific to skeletal muscle tissue, underscoring the importance of appropriate model selection.