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Induced pluripotent stem cells (iPSCs) hold promise for generating personalized xenogenic organs via development of cross-species chimeric animals. However, whether human and other primate iPSCs are capable of establishing cross-species chimeras remains unknown. Recognizing the ethical concerns of cross-species chimerism using human iPSCs, we explored the capacity for cross-species chimerism between distinct, non-human primates. Injection of either pig-tailed macaque iPSCs or chimpanzee iPSCs into the rhesus macaque blastocyst embryos demonstrated that these cells survive, proliferate, and integrate near the rhesus inner cell mass (ICM). Ectopic expression of BCL2 in pig-tailed and chimpanzee iPSCs greatly improved the success rate of establishing cross-species blastocyst chimerism. This study represents the first successful cross-species blastocyst chimerism between distinct, non-human primate species, and highlights critical factors that may be necessary to unlock the broad potential of primate iPSCs to form cross-species chimeras, with diverse applications for basic research and translational medicine.Overall design: A total of 29 samples were used in this study which includes biological and technical replicates from each of the study species. The RNA-seq library preperation and sequencing for all the samples/species were conducted at the same time to minimize potential batch effect. We compared transcriptome profiles of chimpanzee iPSCs, pig-tailed macaque iPSCs, rhesus macaque iPSCs and ESCs with the transcriptome of rhesus macaque and mouse embryonic inner cell mass. |