title: 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.
authors.affiliation: Valencia Node of The National Stem Cell Bank, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Galan
authors.forename: Patricia
authors.initials: P
authors.lastname: Diaz-Gimeno
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Poo
authors.forename: Diana
authors.initials: D
authors.lastname: Valbuena
authors.forename: Eva
authors.initials: E
authors.lastname: Sanchez
authors.forename: Veronica
authors.initials: V
authors.lastname: Ruiz
authors.forename: Joaquin
authors.initials: J
authors.lastname: Dopazo
authors.forename: David
authors.initials: D
authors.lastname: Montaner
authors.forename: Ana
authors.initials: A
authors.lastname: Conesa
authors.forename: Carlos
authors.initials: C
authors.lastname: Simon
mesh_terms: D053624:Blastocyst Inner Cell Mass / Q000166:cytology / Q000378:metabolism; D001757:Blastomeres / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D058977:Molecular Sequence Annotation; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D039901:Totipotent Stem Cells / Q000166:cytology / Q000378:metabolism*