Journal
CELL STEM CELL
Volume 18, Issue 1, Pages 67-72Publisher
CELL PRESS
DOI: 10.1016/j.stem.2015.11.017
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Funding
- National Institutes of Health [1R21ID012228]
- Medical Research Council/British Heart Foundation [G1000847]
- British Heart Foundation
- British Heart Foundation Centre of Regenerative Medicine [RM/13/3/3015]
- MRC [G1000847, G0800784, G0600275] Funding Source: UKRI
- Medical Research Council [G1000847, G0800784, G0600275] Funding Source: researchfish
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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 normalmouse 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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