Chimpanzee and pig-tailed macaque iPSCs: Improved culture and generation of primate cross-species embryos
Morteza Roodgar, Fabian P. Suchy, Lan Huong Nguyen, Vivek K. Bajpai, Rahul Sinha, José G. Vilches-Moure, Kevin Van Bortle, Joydeep Bhadury, Ahmed A. 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, M 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.