Only rodent embryonic stem (ES) cells can self-renew in the pristine state of pluripotency called the naive or ground state. Human ES (hES) cells self-renew in the so-called primed state of pluripotency, which is an obstacle to research, hindering cost-effective cultivation in media devoid of animal-derived products, genetic stability, and genome engineering. Here we show that forced expression of a hormone-dependent STAT3-ERT2, in combination with LIF and inhibitors of MEK and GSK3beta, allows hES cells to escape from the primed state, and enter a new state designated as TL2i, characterized by the activation of STAT3 target genes, regular passaging by single cell dissociation, and the expression of naive state-specific transcription factors.
Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency.
Specimen part, Cell line
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