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Review
. 2019 Jul 15;28(14):897-906.
doi: 10.1089/scd.2019.0057.

On Mammalian Totipotency: What Is the Molecular Underpinning for the Totipotency of Zygote?

Kejin Hu  1
Affiliations
Review

On Mammalian Totipotency: What Is the Molecular Underpinning for the Totipotency of Zygote?

Kejin Hu. Stem Cells Dev. .

Abstract

The mammalian zygote is described as a totipotent cell in the literature, but this characterization is elusive ignoring the molecular underpinnings. Totipotency can connote genetic totipotency, epigenetic totipotency, or the reprogramming capacity of a cell to epigenetic totipotency. Here, the implications of these concepts are discussed in the context of the properties of the zygote. Although genetically totipotent as any diploid somatic cell is, a zygote seems not totipotent transcriptionally, epigenetically, or functionally. Yet, a zygote may retain most of the key factors from its parental oocyte to reprogram an implanted differentiated genome or the zygote genome toward totipotency. This totipotent reprogramming process may extend to blastomeres in the two-cell-stage embryo. Thus, a revised alternative model of mammalian cellular totipotency is proposed, in which an epigenetically totipotent cell exists after the major embryonic genome activation and before the separation of the first two embryonic lineages.

Keywords: blastomere; embryogenesis; embryonic stem cells; epigenetic totipotency; reprogramming; totipotency; zygote.

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Conflict of interest statement

No competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
The paternal and maternal genomes are physically separated, under differential reprogramming, and epigenetically distinct in the mouse zygote. Green, 5-methylcytosine detected with antibody; blue, DNA staining; hours postfertilization are indicated above each image; Left and middle panels, one zygote in each panel with its two separate pronuclei; right panel, a two-cell stage embryo. Small nuclei in the middle and right panels are polar bodies. Note the extensive demethylation of the paternal pronucleus in the zygote 8 h postfertilization in the middle panel, and compartmentalized paternal and maternal chromosomes with differential methylation on cytosines in each of the two-cell blastomeres. Images are courtesy of Thomas Haaf with permission from Nature.
<b>FIG. 2.</b>
FIG. 2.
The totipotent reprogramming activity of an oocyte or a zygote is independent of epigenetic status. Note that, like the united sperm and oocyte genomes, an individual nucleus at distinct differentiated epigenetic states (fibroblasts, T cells, or B cells) can be reprogrammed by an enucleated oocyte, which is lacking any of its own nuclear genetic material, to totipotency and gives rise to an animal.
<b>FIG. 3.</b>
FIG. 3.
A revised model for reprogramming capacity and differentiation potential of an early embryonic cell in comparison with the conventional view [1]. The schema is based on mouse, in which the epigenetic totipotency may exist from the four-cell to the eight-cell embryo before compaction. The time line for other species may vary. Cytoplasmic purple represents the totipotent reprogramming activity of maternal origin. EGA, embryonic genome activation.
See this image and copyright information in PMC

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