title: Tracking the progression of the human inner cell mass during embryonic stem cell derivation.
abstract: The different pluripotent states of mouse embryonic stem cells (ESCs) in vitro have been shown to correspond to stages of mouse embryonic development. For human cells, little is known about the events that precede the generation of ESCs or whether they correlate with in vivo developmental stages. Here we investigate the cellular and molecular changes that occur during the transition from the human inner cell mass (ICM) to ESCs in vitro. We demonstrate that human ESCs originate from a post-ICM intermediate (PICMI), a transient epiblast-like structure that has undergone X-inactivation in female cells and is both necessary and sufficient for ESC derivation. The PICMI is the result of progressive and defined ICM organization in vitro and has a distinct state of cell signaling. The PICMI can be cryopreserved without compromising ESC derivation capacity. As a closer progenitor of ESCs than the ICM, the PICMI provides insight into the pluripotent state of human stem cells.
authors.affiliation: Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium. homas.oleary@ugent.be
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Leary
authors.forename: Björn
authors.initials: B
authors.lastname: Heindryckx
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lierman
authors.forename: David
authors.initials: D
authors.lastname: van Bruggen
authors.forename: Jelle J
authors.initials: JJ
authors.lastname: Goeman
authors.forename: Mado
authors.initials: M
authors.lastname: Vandewoestyne
authors.forename: Dieter
authors.initials: D
authors.lastname: Deforce
authors.forename: Susana M Chuva
authors.initials: SM
authors.lastname: de Sousa Lopes
authors.forename: Petra
authors.initials: P
authors.lastname: De Sutter
mesh_terms: D000818:Animals; D053624:Blastocyst Inner Cell Mass / Q000166:cytology* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D049951:X Chromosome Inactivation; D000099229:RE1-Silencing Transcription Factor
chemical_list: D050814:Octamer Transcription Factor-3; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C000715187:Lin28A protein, human; C494173:POU5F1 protein, human