4.8 Article

Live birth of chimeric monkey with high contribution from embryonic stem cells

Journal

CELL
Volume 186, Issue 23, Pages 4996-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2023.10.005

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By optimizing the culture conditions for monkey naive embryonic stem cells, researchers have successfully generated live chimeric monkeys with high donor cell contribution. This finding has significant implications for the study of primate naive pluripotency and genetic engineering of non-human primates.
A formal demonstration that mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency is the generation of chimeric animals through early embryo complementation with homologous cells. Whereas such naive pluripotency has been well demonstrated in rodents, poor chimerism has been achieved in other species including non-human primates due to the inability of the donor cells to match the developmental state of the host embryos. Here, we have systematically tested various culture conditions for establishing monkey naive embryonic stem cells and optimized the procedures for chimeric embryo culture. This approach generated an aborted fetus and a live chimeric monkey with high donor cell contribution. A stringent characterization pipeline demonstrated that donor cells efficiently (up to 90%) incorporated into various tissues (including the gonads and placenta) of the chimeric monkeys. Our results have major implications for the study of primate naive pluripotency and genetic engineering of non-human primates.

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