Defining the Genomic Signature of Totipotency and Pluripotency during Early Human Development

Abstract

The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation network signature (UNS) and applied it to a differential gene expression profile between single blastomeres from day-3 embryos, ICMs and hESCs. This allowed us to establish a unique signature composed of highly interconnected genes characteristic of totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro pluripotency (107 genes), and which are also proprietary according to functional analysis. This systems biology approach has led to an improved understanding of the molecular and signaling processes governing human pre-implantation embryo development, as well as enabling us to comprehend how hESCs might adapt to in vitro culture conditions.

Partial reprogramming induces a steady decline in epigenetic age before loss of somatic identity

“…To facilitate comparison to other systems and associate eAge with intermediate states in the reprogramming trajectory we compared it to gene expression measured in the same samples. We analysed corresponding microarray expression data for 19 well-established pluripotency marker genes (Table 1 and Supplementary fig.3) as a proxy for reaching a mature pluripotent state (Ginis et al 2004; Cai et al 2006; Mallon et al 2013; Galan et al 2013; Boyer et al 2005). We statistically clustered the expression patterns of those genes (Genolini et al 2015), which resulted in two composite trajectories.…”

Totipotency continuity from zygote to early blastomeres: a model under revision

“…Moreover, in global terms, the two-cell-like stem cells might be transcriptionally more similar to blastocyst cells than blastomeres from the two-cell stage (Kolodziejczyk 2016). A similar approach in humans revealed a set of 61 genes that might constitute a molecular totipotency signature distinguishing the blastomeres of day 3 embryos from pluripotent cells (Galan et al 2013).…”

Nucleosome positioning changes during human embryonic stem cell differentiation

“…INM. Among them, while known and putative pluripotent marker genes (20 in total) 43 are being silenced (P < 2.2e-16), genes related to development, extracellular matrix (ECM), and focal adhesion are being activated (P < 3.0e-11) (Fig. 1B and Table S1A-B).…”