The 21st century started with an important discovery that a pluripotent stem cell can be induced from differentiated cells by 'simply' introducing a few transcription factors. Because pluripotent embryonic stem cells can be stably maintained in culture and also induced, the mechanisms as to how cells maintain and acquire pluripotency have been extensively interrogated. In contrast, how cells maintain or acquire totipotency and the cell potency that exists in the zygote are still poorly understood. To address this question, it is necessary to capture the features that reside in totipotent cells. Here, we review recent results, which shed light on the unique epigenetic state in totipotent cells, and discuss how totipotency is regulated before finding its way towards pluripotency.
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