Abstract
Cell-cultivated meat has emerged as an alternative approach for sustainable protein production, but replicating the texture and complex composition of conventional meat remains a critical challenge. Here, we developed an efficient approach to produce multitissue engineered meat by leveraging a serum- and animal-component-free differentiation system to direct porcine pregastrulation epiblast stem cells toward muscle, adipose, and endothelium with synergistic functions. These three types of cell progenitors demonstrated autonomous intercellular recognition and coculture compatibility in a scaffold-free 3D suspension system, enabling the spontaneous formation of tissue-mimetic spheroids with enhanced cellular multiplication efficiency. The products of multitissue cultivated meat recapitulated the textural properties of conventional pork and allowed for nutritional modulation. This platform overcomes key limitations in currently employed cultured meat technologies by integrating scalable 3D suspension culture with serum-free, species-specific stem cell multidirectional differentiation, providing an avenue for the development of multitissue cell-cultivated meat.
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Data availability
The raw RNA-seq data generated in this paper have been deposited in the Genome Sequence Archive (GSA) at the National Genomics Data Center, China National Center for Bioinformation (NGDC/CNCB), under accession number CRA026288, and are publicly accessible at https://ngdc.cncb.ac.cn/gsa/browse/CRA026288. The data generated in this study are provided in the Supplementary Information/Source Data file. Source data are provided with this paper.
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Acknowledgements
This work was supported by the Biological Breeding-National Science and Technology Major Project (2023ZD0407503 to J.H.), the Natural Science Foundation of China (32370846 to J.H., 31970825 to J.H., 32402757 to M.Z.), the National Key R&D Program of China (2022YFD1302201 to J.H.), the fellowship of China Postdoctoral Science Foundation (2022M720168 to M.Z.), China National Postdoctoral Program for Innovative Talents (BX20220344 to M.Z.), Pinduoduo-China Agricultural University Research Fund (PC2024A01001 to J.H.), the 2115 Talent Development Program of China Agricultural University and High-performance Computing Platform of China Agricultural University.
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J.H. conceptualized this project. J.H., S.C., and A.M. supervised the overall experiments. Y.Y. and G.Z. performed pgEpiSCs culture in vitro and characteristics analysis of differentiated cells. J.H., Y.Y., R.L., and M.Z. coordinated and performed bioinformatics analysis of the RNA-seq sequencing data. Y.Y., G.Z., M.Z., and T.W. performed spheroid culture in vitro and characteristics analysis. J.H., Y.Y., A.M, Y.Z., and Y.C. performed preparation of cell-based meat, nutritional components, and texture analysis. Y.Y., G.Z., L.L., and X.F. completed the preparation, cell inoculation of 3D edible scaffolds, and SEM. M.Z. performed pgEpiSCs derivation. Y.Y., G.Z., T.W., and L.Q. performed flow cytometric analysis. Y.Y., G.Z., Y.W., S.W., and H.Z. performed qRT-PCR primer design, quantitative validation, and immunofluorescence image processing. Y.Y., X.C., and M.Z. performed the preparation of the experimental schematic. J.H. and Y.Y. performed manuscript writing, review, and editing.
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Nature Communications thanks Jinkee Hong, Mark J. Post, and the other anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.
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Yao, Y., Zhu, G., Zhi, M. et al. Generation of multitissue cell-cultivated meat via multidirectional differentiation of stable porcine epiblast stem cells. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70177-w
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DOI: https://doi.org/10.1038/s41467-026-70177-w
