“Pluripotent Stem Cells: Past, Present and Future”

Mouse embryonic stem (ES) cells were derived over 40 years ago and are classed as naïve. Human embryonic stem cells, available since 1998, represent a more advanced stage of pluripotency, termed primed. More recently, human naïve pluripotent stem cells have been derived from embryos and generated by somatic cell reprogramming. Human naïve PSCs share key transcription factors and chromatin features with mouse ES cells yet have distinct self-renewal requirements. The differences relate to the unexpected and unique potency of human naïve PSCs to differentiate into trophectoderm. This reverse differentiation potency can be harnessed to produce structures comprising trophoblast, hypoblast and epiblast that closely resemble the human blastocyst. To produce embryonic lineages, naïve stem cells undergo a formative transition process that mirrors peri- and early post-implantation differentiation of the epiblast.

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