Rat embryonic stem cells produce fertile offspring through tetraploid complementation [RRBS]

Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to their developmental potency. Tetraploid complementation, through which an entire organism is produced from donor pluripotent cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs from other species besides mice can pass this test. Here we show that the rat ESCs at very early passages are also capable to produce fertile offspring by tetraploid complementation, however, this capacity is rapidly lost during culture due to the loss of genomic imprinting. Our findings support that the naïve ground state pluripotency exists in rat and can be captured in rat ESCs, yet may be subjected to species-specific regulations, which have implications for the derivation and application of naïve pluripotent stem cells in other species including human.