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

Kejin Hu

doi:10.1089/scd.2019.0057

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.

Highlights

As a critical starting point of a mammalian life, the zygote is described in the literature as being totipotent [1,2,3,4]
Every normal diploid cell is of genetic totipotency; epigenetic totipotency may exist in embryonic cells immediately before the separation of the first two embryonic lineages
Zygote uniquely retains most of the totipotent reprogramming activity of the oocyte

Summary

Introduction

As a critical starting point of a mammalian life, the zygote is described in the literature as being totipotent [1,2,3,4]. Upon fertilization of an oocyte, the paternal and maternal chromatin starts epigenetic and transcriptional reprogramming to totipotency by the oocyte factors This totipotent reprogramming process continues beyond the zygote; even a blastomere from a two-cell stage embryo retains significant capacity for totipotent reprogramming [76,77]. The totipotent reprogramming activity in oocyte and zygote is independent of their epigenetic status because an enucleated oocyte can reprogram into totipotency the fully differentiated implanted genomes of various origins, including those from fibroblasts [79], cumulus [19], Sertoli cells [80], T cells, B cells [81], and others (Fig. 2). The totipotency of a blastomere from the two-cell stage embryo may be largely maternal since it still retains a significant amount of oocyte factors

A Revised Model for Cellular Totipotency

Conclusions and Prospects