Primate embryogenesis predicts the hallmarks of human naïve pluripotency

Abstract

Naïve 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 naïve state is inherently linked to preimplantation epiblast identity in the embryo. We hypothesise that distinctive features of primate development provide stringent criteria to evaluate naïve pluripotency in human and other primate cells. Based on our hypothesis, we define 12 key hallmarks of naïve pluripotency, five of which are specific to primates. These hallmarks may serve as a functional framework to assess human naïve ESCs.

Keywords: Amnion; Epiblast; Extraembryonic; Naïve pluripotency; Postimplantation; Primate.

Fig. 1.

Schematic overview of rodent and primate development from fertilisation to gastrulation. Developmental time of rodent development (A) and primate development (B) is given in Carnegie stages to facilitate comparison between species. Embryonic lineages are represented in blue shades, extraembryonic lineages in red shades. Cartoons for primate development were drawn based on histological sections of common marmoset (Moore et al., 1985), rhesus macaque (Enders and King, 1988; Enders et al., 1986) and early human stages of the Carnegie collection (Hertig and Rock, 1941, 1946, 1949; Rock and Hertig, 1948). Note that extraembryonic mesoderm specification from visceral endoderm is exclusively based on electron micrographs of early rhesus macaque implantation stages.

Fig. 2.

Images of early primate implantation stages. Carnegie stages 5 and 6 are shown from (A,D) common marmoset (Enders and Lopata, 1999), (B,E) rhesus macaque (Enders et al., 1986) and (C,F) human stages of the Carnegie collection (Hertig and Rock, 1941; O'Rahilly and Muller, 1987). Blue arrowheads indicate postimplantation epiblast (A-C) or embryonic disc (D-F), red arrowheads indicate amniotic epithelial cells. Images reproduced with permission from John Wiley and Sons (A,B,D,E) and the Carnegie Institution of Washington (C,F).

Fig. 3.

Hallmarks of naïve pluripotency in primates. (A) White circles symbolise hallmarks of naïve pluripotency in both rodents and primates, turquoise circles are specific to primates. (B) Grey circles encompass known features of the rodent preimplantation epiblast, which have not yet been analysed in primate embryos. TE, transposable element.