Chimpanzee and pig-tailed macaque iPSCs: Improved culture and generation of primate cross-species embryos

黑猩猩和豚尾猕猴诱导多能干细胞:灵长类跨物种胚胎培养和生成的改进

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作者:Morteza Roodgar ,Fabian P Suchy ,Lan H Nguyen ,Vivek K Bajpai ,Rahul Sinha ,Jose G Vilches-Moure ,Kevin Van Bortle ,Joydeep Bhadury ,Ahmed Metwally ,Lihua Jiang ,Ruiqi Jian ,Rosaria Chiang ,Angelos Oikonomopoulos ,Joseph C Wu ,Irving L Weissman ,Joseph L Mankowski ,Susan Holmes ,Kyle M Loh ,Hiromitsu Nakauchi ,Catherine A VandeVoort ,Michael P Snyder

Abstract

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. Keywords: CP: Developmental biology; Nonhuman primates; blastocyst, BCL2; chimpanzee; cross-species embryos; iPSCs; interspecies chimera; pig-tailed macaque.

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