From quiescence to hypertrophy: existing and emerging genetic targets to fine-tune myogenesis in cultivated muscle.

Cultivated meat (CM) offers a promising alternative to conventional meat with the potential to address the sustainability, animal welfare, and public health concerns associated with intensive animal agriculture. The scalability, economic viability and quality of a CM product are likely to be reliant on high-performing muscle cell lines capable of rapid proliferation, efficient differentiation and a high protein yield relative to culture volume. Although early research has prioritised the expansion of undifferentiated cell biomass, differentiated muscle cells will likely be important for replicating the structural and nutritional properties of conventional meat. Cell line engineering offers a powerful method to achieve this by enabling precise control over cellular functions while reducing the cost and complexity of a bioprocess. To date, cell line engineering has been deployed in the context of CM to improve cell characteristics, such as immortality, proliferation rate, or metabolic efficiency. However, many of the complex signalling pathways that regulate myogenesis and skeletal muscle hypertrophy remain underexplored in agriculturally-relevant cell lines. This review explores the key existing and emerging genetic targets for enhancing myogenesis in the context of CM, including TGF-β, MEK/ERK, PI3K/AKT/mTOR and Wnt signalling pathways. Engineering these pathways has the potential to fine-tune the balance between proliferation and differentiation or induce hypertrophy and increase protein yield without the need for costly media additives. The integration of advanced genome editing technologies with rigorous quality control and regulatory systems could significantly improve the performance of muscle-derived cells for scalable CM production.