title: Generation of human female reproductive tract epithelium from human embryonic stem cells.
abstract: BACKGROUND
  Recent studies have identified stem/progenitor cells in human and mouse uterine epithelium, which are postulated to be responsible for tissue regeneration and proliferative disorders of human endometrium. These progenitor cells are thought to be derived from Müllerian duct (MD), the primordial female reproductive tract (FRT).
  
  
  RESULTS
  We have developed a model of human reproductive tract development in which inductive neonatal mouse uterine mesenchyme (nMUM) is recombined with green fluorescent protein (GFP)-tagged human embryonic stem cells (hESCs); GFP-hESC (ENVY). We demonstrate for the first time that hESCs can be differentiated into cells with a human FRT epithelial cell phenotype. hESC derived FRT epithelial cells emerged from cultures containing MIXL1(+) mesendodermal precursors, paralleling events occurring during normal organogenesis. Following transplantation, nMUM treated embryoid bodies (EBs) generated epithelial structures with a typical MD phenotype that expressed the MD markers PAX2, HOXA10. Functionally, the hESCs derived FRT epithelium responded to exogenous estrogen by proliferating and secreting uterine-specific glycodelin A (GdA).
  
  
  CONCLUSIONS
  These data show nMUM can induce differentiation of hESC to form the FRT epithelium. This may provide a model to study early developmental events of the human FRT.
authors.affiliation: The Ritchie Centre, Monash Institute of Medical Research and Department of Obstetrics and Gynecology, Monash University, Melbourne, Australia.
authors.forename: Louie
authors.initials: L
authors.lastname: Ye
authors.forename: Robyn
authors.initials: R
authors.lastname: Mayberry
authors.forename: Camden Y
authors.initials: CY
authors.lastname: Lo
authors.forename: Kara L
authors.initials: KL
authors.lastname: Britt
authors.forename: Edouard G
authors.initials: EG
authors.lastname: Stanley
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Elefanty
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Gargett
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D005836:Genitalia, Female / Q000166:cytology / Q000254:growth & development*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction
chemical_list: D049452:Green Fluorescent Proteins