title: Human hypoblast formation is not dependent on FGF signalling.
abstract: Mouse embryos segregate three different lineages during preimplantation development: trophoblast, epiblast and hypoblast. These differentiation processes are associated with restricted expression of key transcription factors (Cdx2, Oct4, Nanog and Gata6). The mechanisms of segregation have been extensively studied in the mouse, but are not as well characterised in other species. In the human embryo, hypoblast differentiation has not previously been characterised. Here we demonstrate co-exclusive immunolocalisation of Nanog and Gata4 in human blastocysts, implying segregation of epiblast and hypoblast, as in rodent embryos. However, the formation of hypoblast in the human is apparently not dependent upon FGF signalling, in contrast to rodent embryos. Nonetheless, the persistence of Nanog-positive cells in embryos following treatment with FGF inhibitors is suggestive of a transient naïve pluripotent population in the human blastocyst, which may be similar to rodent epiblast and ES cells but is not sustained during conventional human ES cell derivation protocols.
authors.affiliation: Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge CB2 1QR, UK.
authors.forename: Mila
authors.initials: M
authors.lastname: Roode
authors.forename: Kathryn
authors.initials: K
authors.lastname: Blair
authors.forename: Philip
authors.initials: P
authors.lastname: Snell
authors.forename: Kay
authors.initials: K
authors.lastname: Elder
authors.forename: Sally
authors.initials: S
authors.lastname: Marchant
authors.forename: Austin
authors.initials: A
authors.lastname: Smith
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nichols
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D046149:Embryo Culture Techniques; D047108:Embryonic Development; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005855:Germ Layers / Q000166:cytology / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D051381:Rats; D015398:Signal Transduction
chemical_list: D005346:Fibroblast Growth Factors; D048049:Extracellular Signal-Regulated MAP Kinases
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