title: The post-inner cell mass intermediate: implications for stem cell biology and assisted reproductive technology.
abstract: BACKGROUND
  Until recently, the temporal events that precede the generation of pluripotent embryonic stem cells (ESCs) and their equivalence with specific developmental stages in vivo was poorly understood. Our group has discovered the existence of a transient epiblast-like structure, coined the post-inner cell mass (ICM) intermediate or PICMI, that emerges before human ESC (hESCs) are established, which supports their primed nature (i.e. already showing some predispositions towards certain cell types) of pluripotency.
  
  
  METHODS
  The PICMI results from the progressive epithelialization of the ICM and it expresses a mixture of early and late epiblast markers, as well as some primordial germ cell markers. The PICMI is a closer progenitor of hESCs than the ICM and it can be seen as the first proof of why all existing hESCs, until recently, display a primed state of pluripotency.
  
  
  RESULTS
  Even though the pluripotent characteristics of ESCs differ from mouse (naïve) to human (primed), it has recently been shown in mice that a similar process of self-organization at the transition from ICM to (naïve) mouse ESCs (mESCs) transforms the amorphous ICM into a rosette of polarized epiblast cells, a mouse PICMI. The transient PICMI stage is therefore at the origin of both mESCs and hESCs. In addition, several groups have now reported the conversion from primed to the naïve (mESCs-like) hESCs, broadening the pluripotency spectrum and opening new opportunities for the use of pluripotent stem cells.
  
  
  CONCLUSIONS
  In this review, we discuss the recent discoveries of mouse and human transient states from ICM to ESCs and their relation towards the state of pluripotency in the eventual stem cells, being naïve or primed. We will now further investigate how these intermediate and/or different pluripotent stages may impact the use of human stem cells in regenerative medicine and assisted reproductive technology.
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FAST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium.
authors.forename: Margot
authors.initials: M
authors.lastname: Van der Jeught
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FAST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium Present address: Coastal Fertility Specialists, 1375 Hospital Drive, Mt Pleasant, SC 29464, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Leary
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FAST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium Present address: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Galbha
authors.initials: G
authors.lastname: Duggal
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FAST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium.
authors.forename: Petra
authors.initials: P
authors.lastname: De Sutter
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FAST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.
authors.forename: Susana
authors.initials: S
authors.lastname: Chuva de Sousa Lopes
authors.affiliation: Ghent Fertility and Stem Cell Team (G-FAST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium bjorn.heindryckx@ugent.be.
authors.forename: Björn
authors.initials: B
authors.lastname: Heindryckx
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001755:Blastocyst / Q000166:cytology; D053624:Blastocyst Inner Cell Mass / Q000166:cytology*; D053595:Embryonic Stem Cells / Q000166:cytology; D005855:Germ Layers / Q000166:cytology*; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology*; D027724:Reproductive Techniques, Assisted
chemical_list: D015415:Biomarkers
keywords: embryonic stem cells; pluripotent states; post-inner cell mass intermediate; regenerative medicine