Generation of human female reproductive tract epithelium from human embryonic stem cells.

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 prim...

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Main Authors: Louie Ye, Robyn Mayberry, Camden Y Lo, Kara L Britt, Edouard G Stanley, Andrew G Elefanty, Caroline E Gargett
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3115988?pdf=render
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author Louie Ye
Robyn Mayberry
Camden Y Lo
Kara L Britt
Edouard G Stanley
Andrew G Elefanty
Caroline E Gargett
author_facet Louie Ye
Robyn Mayberry
Camden Y Lo
Kara L Britt
Edouard G Stanley
Andrew G Elefanty
Caroline E Gargett
author_sort Louie Ye
collection DOAJ
description 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). METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
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spelling doaj.art-c49d54c8c7014be3a2210e55d76248e32022-12-21T22:32:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2113610.1371/journal.pone.0021136Generation of human female reproductive tract epithelium from human embryonic stem cells.Louie YeRobyn MayberryCamden Y LoKara L BrittEdouard G StanleyAndrew G ElefantyCaroline E GargettBACKGROUND: 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). METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.http://europepmc.org/articles/PMC3115988?pdf=render
spellingShingle Louie Ye
Robyn Mayberry
Camden Y Lo
Kara L Britt
Edouard G Stanley
Andrew G Elefanty
Caroline E Gargett
Generation of human female reproductive tract epithelium from human embryonic stem cells.
PLoS ONE
title Generation of human female reproductive tract epithelium from human embryonic stem cells.
title_full Generation of human female reproductive tract epithelium from human embryonic stem cells.
title_fullStr Generation of human female reproductive tract epithelium from human embryonic stem cells.
title_full_unstemmed Generation of human female reproductive tract epithelium from human embryonic stem cells.
title_short Generation of human female reproductive tract epithelium from human embryonic stem cells.
title_sort generation of human female reproductive tract epithelium from human embryonic stem cells
url http://europepmc.org/articles/PMC3115988?pdf=render
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