Primate embryogenesis predicts the hallmarks of human naive pluripotency

Naive pluripotent mouse embryonic stem cells (ESCs) resemble the preimplantation epiblast and efficiently contribute to chimaeras. Primate ESCs correspond to the postimplantation embryo and fail to resume development in chimaeric assays. Recent data suggest that human ESCs can be 'reset' to an earlier developmental stage, but their functional capacity remains ill defined. Here, we discuss how the naive state is inherently linked to preimplantation epiblast identity in the embryo. We hypothesise that distinctive features of primate development provide stringent criteria to evaluate naive pluripotency in human and other primate cells. Based on our hypothesis, we define 12 key hallmarks of naive pluripotency, five of which are specific to primates. These hallmarks may serve as a functional framework to assess human naive ESCs.