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Efficient derivation of transgene-free porcine induced pluripotent stem cells enables in vitro modeling of species-specific developmental timing

ABSTRACT: Sus domesticus (pig) are an excellent large mammalian model for comparative studiesdue to their relatively comparable physiology and organ size to humans. The derivation of transgene-free porcine pluripotent stem cells (PiPSCs) will therefore benefit the development of porcine-specific models for regenerative biology and its medical applications. In the past, this effort has been hampered by a lack of understanding of the signaling milieu that stabilizes the porcine pluripotent state in vitro. Here, we report that transgene-free PiPSCs can be efficiently derived from porcine fibroblasts by episomal vectors along with microRNA-302/367 using optimized protocols tailored for this species. Established PiPSCs can robustly differentiate into derivates representing the primary germ layers in vitro and in vivo. Furthermore, the transgene- free PiPSCs preserve intrinsic species-specific developmental timing in culture. This capacity is demonstrated by establishing a porcine in vitro segmentation clock model that, for the first time, displays a specific periodicity at ~ 3.7 hours, a time scale recapitulating in vivo porcine somitogenesis. We therefore propose that these transgene-free PiPSCs can serve as a powerful tool for modeling development and disease, informing both conserved and unique features of mammalian pluripotency and developmental timing mechanisms.

ORGANISM(S): Sus scrofa

PROVIDER: GSE227985 | GEO | 2023/11/09

REPOSITORIES: GEO

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