Transdifferentiation of fibroblasts into muscle cells to constitute cultured meat with tunable intramuscular fat deposition

• DOI: 10.7554/elife.93220
• Publication Date: 2024-01-22T11:25:10Z
• Authors: Tongtong Ma; Ruimin Ren; Jianqi Lv; Ruipeng Yang; Xinyi Zheng; Yang Hu; Guiyu Zhu; Heng Wang
• Keywords: Sustainable Diets and Environmental Impact; Muscle Protein Synthesis; 0301 basic medicine; Cell biology; Meat; muscle; transdifferentiation; QH301-705.5; Science; Deposition (geology); Muscle Development; intramuscular fat; Agricultural and Biological Sciences; Food science; meat; 03 medical and health sciences; Biochemistry, Genetics and Molecular Biology; Animals; Biology (General); Muscle, Skeletal; Biology; Cell Proliferation; Muscle Cells; Transdifferentiation; Stem cell; Ecology; Q; R; Life Sciences; Paleontology; Intramuscular fat; Cell Biology; Fibroblasts; Chemistry; Protein Metabolism in Exercise and Nutrition; Metabolism; Adipose Tissue; FOS: Biological sciences; Cell Transdifferentiation; Environmental Science; Physical Sciences; Myocyte; Medicine; Animal Science and Zoology; Sediment; In Vitro Meat; Factors Affecting Meat Quality and Preservation; Chickens

Current studies on cultured meat mainly focus on the muscle tissue reconstruction in vitro, but lack the formation of intramuscular fat, which is a crucial factor in determining taste, texture, and nutritional contents. Therefore, incorporating fat into cultured meat is of superior value. In this study, we employed the myogenic/lipogenic transdifferentiation of chicken fibroblasts in 3D to produce muscle mass and deposit fat into the same cells without the co-culture or mixture of different cells or fat substances. The immortalized chicken embryonic fibroblasts were implanted into the hydrogel scaffold, and the cell proliferation and myogenic transdifferentiation were conducted in 3D to produce the whole-cut meat mimics. Compared to 2D, cells grown in 3D matrix showed elevated myogenesis and collagen production. We further induced fat deposition in the transdifferentiated muscle cells and the triglyceride content could be manipulated to match and exceed the levels of chicken meat. The gene expression analysis indicated that both lineage-specific and multifunctional signalings could contribute to the generation of muscle/fat matrix. Overall, we were able to precisely modulate muscle, fat, and extracellular matrix contents according to balanced or specialized meat preferences. These findings provide new avenues for customized cultured meat production with desired intramuscular fat contents that can be tailored to meet the diverse demands of consumers.