title: Human-Mouse Chimerism Validates Human Stem Cell Pluripotency.
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.
authors.affiliation: The Anne McLaren Laboratory, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Department of Surgery and British Heart Foundation Centre of Regenerative Medicine, University of Cambridge, Cambridge, CB2 0SZ, UK. Electronic address: vlm37@cam.ac.uk.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Mascetti
authors.affiliation: The Anne McLaren Laboratory, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Department of Surgery and British Heart Foundation Centre of Regenerative Medicine, University of Cambridge, Cambridge, CB2 0SZ, UK.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Pedersen
mesh_terms: D000818:Animals; D019521:Body Patterning; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D046528:Chimerism; D053595:Embryonic Stem Cells / Q000166:cytology*; D005775:Gastrula / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D044968:Regenerative Medicine; D013045:Species Specificity