Defining the Genomic Signature of Totipotency and Pluripotency during Early Human DevelopmentReportar como inadecuado

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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.

Autor: Amparo Galan, Patricia Diaz-Gimeno, Maria Eugenia Poo, Diana Valbuena, Eva Sanchez, Veronica Ruiz, Joaquin Dopazo, David Montaner



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