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Human-Mouse Chimerism Validates Human Stem Cell Pluripotency.


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Type

Article

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Authors

Mascetti, Victoria L 
Pedersen, Roger A 

Abstract

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.

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Keywords

Animals, Body Patterning, Cell Culture Techniques, Cell Differentiation, Cell Lineage, Cell Proliferation, Cells, Cultured, Chimerism, Embryonic Stem Cells, Gastrula, Humans, Induced Pluripotent Stem Cells, Mice, Regenerative Medicine, Species Specificity

Journal Title

Cell Stem Cell

Conference Name

Journal ISSN

1934-5909
1875-9777

Volume Title

18

Publisher

Elsevier BV
Sponsorship
Medical Research Council (G1000847)
Medical Research Council (G0800784)
Medical Research Council (G0600275)
Wellcome Trust (097922/Z/11/B)
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.