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As our closest living relatives, non-human primates uniquely enable explorations of human health, disease, development, and evolution. Considerable effort has thus been devoted to generating induced pluripotent stem cells (iPSCs) from multiple non-human primate species. Here, we establish improved culture methods for chimpanzee (Pan troglodytes) and pig-tailed macaque (Macaca nemestrina) iPSCs. Such iPSCs spontaneously differentiate in conventional culture conditions, but can be readily propagated by inhibiting endogenous WNT signaling. As a unique functional test of these iPSCs, we injected them into the pre-implantation embryos of another non-human species, rhesus macaques (Macaca mulatta). Ectopic expression of gene BCL2 enhances the survival and proliferation of chimpanzee and pig-tailed macaque iPSCs within the pre-implantation embryo, although the identity and long-term contribution of the transplanted cells warrants further investigation. In summary, we disclose transcriptomic and proteomic data, cell lines, and cell culture resources that may be broadly enabling for non-human primate iPSCs research.
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•Inhibiting WNT signaling improves culture of chimp and pig-tailed macaque iPSCs•Endogenous high expression of BCL2 in the rhesus inner cell mass•Expression of BCL2 enhances proliferation of chimp iPSCs in rhesus early embryo•Co-culture of chimp and human iPSCs can differentiate into integrated cardiomyocytes
Roodgar et al. demonstrate an improved culture of chimpanzee and pig-tailed macaque iPSCs. They show high expression of endogenous BCL2 in rhesus macaque ICM. Through over expression of BCL2 in chimpanzee iPSCs, they generate primate cross-species pre-implantation embryos composed of chimpanzee iPSCs and rhesus pre-implantation embryos.