Mascetti, V.L. and Pedersen, R.A. Cell Stem Cell 18, 1–6 (2016).

Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are considered pluripotent because of their ability to differentiate into most embryonic cell types in vitro. But a more stringent test for pluripotency—the ability to contribute to all tissues in a developing embryo—has been assessed only in mouse pluripotent cells, for obvious reasons. Mascetti and Pedersen have now applied a similar standard to human cells by generating stage-matched interspecies chimeras in the mouse. They transplanted three hiPSC and two hESC fluorescently labeled lines into gastrula-stage embryos and found high (70–100%) tissue incorporation across all fetal subregions, similar to observations with murine epiblast stem cells. The work establishes the mapping of human tissue contribution to murine chimeras as an in vivo test for stem cell pluripotency.