State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Proc Natl Acad Sci U S A. 2017 Nov 7;114(45):11974-11979. doi: 10.1073/pnas.1708710114. Epub 2017 Oct 23.
Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to the developmental potency. Tetraploid complementation, through which an entire organism is produced from the pluripotent donor cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs of other species besides mice can pass this test. Here we show 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, they lose this capacity rapidly during culture due to a nearly complete loss of genomic imprinting. Our findings support that the naïve ground state pluripotency can be captured in rat ESCs but also point to the species-specific differences in its regulation and maintenance, which have implications for the derivation and application of naïve pluripotent stem cells in other species including human.
胚胎干细胞（ESCs）的多能性可以根据其发育潜能进行功能评估。通过四倍体补偿，即用多能供体细胞产生整个生物体，被视为多能性的最严格测试。目前尚不清楚除了小鼠之外的其他物种的 ESCs 是否能够通过该测试。在这里，我们表明，在非常早期的传代中处于 2i（两种小分子抑制剂）条件下的大鼠 ESCs 能够通过四倍体补偿产生可育后代。然而，由于基因组印记几乎完全丢失，它们在培养过程中迅速失去这种能力。我们的研究结果支持原始状态的多能性可以在大鼠 ESCs 中捕获，但也指出其在调节和维持方面的物种特异性差异，这对原始多能干细胞在包括人类在内的其他物种中的衍生和应用具有重要意义。
