Parsing the pluripotency continuum in humans and non-human primates for interspecies chimera generation

Pluripotency refers to the potential of single cells to form all cells and tissues of an organism. The observation that pluripotent stem cells can chimerize the embryos of evolutionarily distant species, albeit at very low efficiencies, could with further modifications, facilitate the production of human-animal interspecies chimeras. The generation of human-animal interspecies chimeras, if achieved, will enable practitioners to recapitulate pathologic human tissue formation in vivo and produce patient-specific organs inside livestock species. However, little is known about the nature of chimera-competent cellular states in primates. Here, I discuss recent advances in our understanding of the pluripotency continuum in humans and non-human primates (NHPs). Although undefined differences between humans and NHPs still justify the utility of studying human cells, the complementary use of NHP PS cells could also allow one to conduct pilot studies testing interspecies chimera generation strategies with reduced ethical concerns associated with human interspecies neurological chimerism. However, the availability of standardized, high-quality and validated NHP PS cell lines covering the spectrum of primate pluripotent states is lacking. Therefore, a clearer understanding of the primate pluripotency continuum will facilitate the complementary use of both human and NHP PS cells for testing interspecies organogenesis strategies, with the hope of one day enabling human organ generation inside livestock species.