Distinct Myogenic Stages Recapitulate Transcriptomic Networks in COPD Cachexia.

Area of Science:

• Biomedical Science
• Genomics
• Cell Biology

Background:

• Cachexia, a complication of Chronic Obstructive Pulmonary Disease (COPD), involves weight loss and muscle wasting.
• Investigating COPD-cachexia requires understanding skeletal muscle gene expression.
• Human muscle-derived cultures (HMDC) offer a potential alternative to invasive muscle biopsies for research.

Purpose of the Study:

• To determine if transcriptomic signatures of COPD-cachexia in bulk skeletal muscle are preserved in HMDC.
• To evaluate the utility of myoblasts, myocytes, and myotubes for studying COPD-cachexia.
• To identify specific gene expression patterns relevant to COPD-cachexia in vitro.

Main Methods:

• Collected vastus lateralis biopsies from COPD, COPD-cachexia, and control participants.
• Isolated satellite cells and differentiated them into myoblasts, myocytes, and myotubes.
• Utilized RNA-sequencing, differential gene expression analysis, and Weighted Gene Co-expression Network Analysis (WGCNA).

Main Results:

• 1,379 genes were differentially expressed in COPD vs. controls; 632 genes in COPD with vs. without cachexia.
• WGCNA identified modules significantly correlated with COPD-cachexia, with specific modules preserved in myoblasts and myocytes.
• Preserved modules were enriched for genes involved in metabolic and inflammatory processes, atrophy, and regeneration.

Conclusions:

• HMDC, particularly myocytes and myoblasts, can serve as in vitro models for COPD-cachexia.
• The study demonstrates the preservation of key transcriptomic signatures in HMDC.
• These findings support the use of HMDC for mechanistic research into COPD-cachexia pathways.