Post Doctoral Researcher Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou, Guangdong, China
Abstract: Guinea pigs serve as valuable models for human disease research, yet the lack of established pluripotent stem cell (PSC) lines has limited their utility in biomedical applications. In this study, we report the first-ever capture of primed pluripotency in guinea pigs through the successful derivation of guinea pig epiblast stem cells (gpEpiSCs) from post-implantation embryos. These cells exhibit stable self-renewal, differentiation into the three germ layers, and normal karyotypes, marking a significant breakthrough in stem cell research. Transcriptomic and epigenetic analyses confirm that gpEpiSCs share key features with human and mouse primed stem cells while also revealing species-specific pluripotency characteristics. We demonstrate that gpEpiSCs rely on FGF2 and ACTIVIN A signaling, with WNT inhibition essential for maintaining their pluripotency state. This pioneering achievement establishes a novel pluripotent model, broadening the landscape of stem cell research and expanding the potential of guinea pigs as preclinical models for disease modeling, regenerative medicine, and drug discovery. The successful establishment of gpEpiSCs unlocks new possibilities for comparative pluripotency studies and translational research, positioning guinea pigs as an indispensable tool for biomedical innovation.
Funding Source: This work was supported in part by the National Key R&D Program of China (2018YFE0204800), NSFC (U20A2013, 32370791, 32100594, and 32200695), Guangdong Basic and Applied Basic Research Foundation ( 2020A1515110122)