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.

Lineage Establishment and Progression within the Inner Cell Mass of the Mouse Blastocyst Requires FGFR1 and FGFR2

“…PrE-biased cells sequentially activate PrE-specific transcription factors, including Sox17, Gata4 and Sox7 , and their downstream targets, such as Lama1 and Col4a1 , ensuring acquisition of apical-basal polarity leading to epithelialization (Artus et al, 2011; Gerbe et al, 2008; Ohnishi et al, 2014). Concomitantly EPI cells mature exhibiting restricted expression of OCT4 and SOX2, and downregulating NANOG (Boroviak and Nichols, 2017; Smith, 2017). …”

Cooperative genetic networks drive a mammalian cell state transition

“…We present evidence that mammalian development, employs a similar regulatory network operating with similar mechanisms (Boroviak and Nichols, 2017;Rossant and Tam, 2017).…”

Naive Pluripotent Stem Cells as a Model for Studying Human Developmental Epigenomics: Opportunities and Limitations

“…Importantly, several epigenomic hallmarks are also used to categorize naive hESCs, such as the presence of two active X-chromosomes in female cells, and global DNA hypomethylation [3,13]. These defining epigenetic characteristics satisfy expectations based on the available human embryo data, and provide exciting opportunities for further study.…”

“…Although derived from epiblast cells of the preimplantation human embryo, the biological properties of hESCs more closely reflect the early postimplantation embryo that is formed several days later in development [2][3][4][5]. This distinction in timing is important because it helps to evaluate the characteristics of hESCs by comparing with their equivalent cells in vivo.…”

“…The criteria include transcriptional profiles, metabolic activity, cell-surface protein expression and signaling responses [3,12,13]. Reassuringly, naive hESC-associated pluripotency factors are detected in human and primate preimplantation epiblast cells, providing support that naive hESC lines maintained in certain conditions can recapitulate the gene expression program of epiblast cells in vivo [2,14,15].…”