Pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), with the capacity to generate any type of cells of the body, have been broadly applied in studying developmental biology, genome engineering, and regenerative medicine.

Tetraploid complementation is considered as the most stringent test to evaluate the developmental potency of pluripotent stem cells. Previously, only mouse ESCs and iPSCs were shown to pass this test.

Recently, rat ESCs derived by the team of Prof. ZHOU Qi from Institute of Zoology of the Chinese Academy of Sciences (CAS), showed the capacity to produce live rats via tetraploid complementation.

In this work, Prof. ZHOU and his team showed that the rat ESCs derived under 2i (two small molecule inhibitors) conditions at very early passages are able to produce fertile offspring by tetraploid complementation. However, the ESCs lost such capacity rapidly during culture, probably due to the nearly complete loss of genomic imprinting.

Although both mouse and rat ESCs exhibited impaired developmental potential after prolonged culture under the 2i/LIF condition, the impairment of developmental capacity progressed much faster in rats than in mice.

The findings may facilitate the understanding of evolution and regulation of pluripotency across mammalian species.

The relevant paper entitled "Rat embryonic stem cells produce fertile offspring through tetraploid complementation" is published online in PNAS.

The work was supported by grants from the National Natural Science Foundation of China, the Ministry of Science and Technology of China, and the Strategic Priority Research Program of the Chinese Academy of Sciences.

Rat embryonic stem cells produce fertile offspring through tetraploid complementation (Image by IOZ)