Human-Mouse Chimerism Validates Human Stem Cell Pluripotency
Cell Stem Cell
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Mascetti, V., & Pedersen, R. (2015). Human-Mouse Chimerism Validates Human Stem Cell Pluripotency. Cell Stem Cell, 18 67-72. https://doi.org/10.1016/j.stem.2015.11.017
Pluripotent stem cells are defined by their capacity to differentiate into all three tissue layers that comprise the body. Chimera formation, generated by stem cell transplantation to the embryo, is a stringent assessment of stem cell pluripotency. However, the ability of human pluripotent stem cells (hPSCs) to form embryonic chimeras remains in question. Here we show using a stage-matching approach that human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) have the capacity to participate in normal mouse development when transplanted into gastrula-stage embryos, providing in vivo functional validation of hPSC pluripotency. hiPSCs and hESCs form interspecies chimeras with high efficiency, colonize the embryo in a manner predicted from classical developmental fate mapping, and differentiate into each of the three primary tissue layers. This faithful recapitulation of tissue-specific fate post-transplantation underscores the functional potential of hPSCs and provides evidence that human-mouse interspecies developmental competency can occur.
This work was supported by National Institutes of Health grant No. 1R21ID012228 (R.A.P.); Medical Research Council/British Heart Foundation grant No. G1000847 (R.A.P.); British Heart Foundation Ph.D. studentship (V.L.M.); British Heart Foundation Centre of Regenerative Medicine (Oxford grant RM/13/3/3015); core support from the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute; and the Cambridge NIHR Biomedical Research Centre.
External DOI: https://doi.org/10.1016/j.stem.2015.11.017
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253540
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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