Professor China Agricultural University Beijing, Beijing, China
Abstract: Cellular cultivated meat (CM) as a sustainable meat production method holds significant potential to reduce challenges associated with environmental sustainability, global public health, and animal welfare. The acquisition of seed cells is a key aspect in the research and application of CM, and embryonic pluripotent stem cells (EPSCs), with their potential for continuous self-renewal and multi-directional differentiation, are considered ideal seed cells for CM development. However, long-term stable passage and directed differentiation of these cells in vitro have always been technical bottlenecks. Guided by insights from a large-scale single-cell transcriptome analysis of preimplantation embryos, we successfully established technical systems for isolation and culture of porcine, bovine, and sheep stable EPSCs, which enables long-term stable passage of EPSCs (over hundred generations) while maintaining pluripotency and genomic stability. Impotently, using these pig EPSCs, we developed a serum-free directed induction differentiation system, and achieve serum-free myogenic differentiation of the EPSCs. The EPSC-derived muscle progenitor cells and muscle fibers show typical muscle cell characteristics and display skeletal muscle transcriptional features. We further establish a three-dimensional differentiation system for shaping cultured tissue by screening plant-based edible scaffolds of non-animal origin, followed by the generation of EPSC-derived cultured meat. Additionally, we further realized the directed induction differentiation of PSCs into multiple tissues such as fat and endothelium, providing possibilities for the creation of nutritionally customized CM. We hope that our study could enrich our understanding for the self-renewal mechanisms of pluripotent stem cells between different species, as well as for the application of stem cells in the food field.
Funding Source: This work was supported by the Biological Breeding-National Science and Technology Major Project (2023ZD04075).