Devising a cell culture method that maintains human pluripotent stem cells (PSCs) in a state similar to naive mouse embryonic stem cells (ESCs) has been a much sought after goal in recent years. Here I consider the historical background to this quest and ask why it is considered consequential. A recent flurry of reports has described a strangely diverse set of endpoints in a search for what has become something of a Holy Grail in contemporary stem cell biology: a cell culture method that maintains human pluripotent stem cells (PSCs) in a state similar to that of naive mouse embryonic stem cells (ESCs). Here I consider the historical background to this quest and ask why it is considered consequential. I assess the methodologies used to derive and maintain the cells and the benchmarks used by various investigators to gauge the success of their efforts, and I finally place the findings in the context of recent analyses of pluripotent stem cell populations at the single-cell level.
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