Abstract

Significance We report on generation of nontransgenic, naïve human pluripotent cells that represent the developmentally earliest state described for human established cells. Existing human ES cell lines in the later primed state can be toggled in reverse to naïve by exposure to histone deacetylase inhibitors prior to naïve culture. A new line was established directly from an eight-cell embryo under naïve culture conditions. We describe the naïve state in humans and show that naïve human ES cells have expanded endoderm developmental capacity.