• Open Access

Estrogen and progesterone together expand murine endometrial epithelial progenitor cells§

Authors

  • Deanna M. Janzen,

    1. Department of Obstetrics and GynecologyUniversity of California, Los Angeles, California, USA
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  • Donghui Cheng,

    1. The Howard Hughes Medical InstituteUniversity of California, Los Angeles, California, USA
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  • Amanda M. Schafenacker,

    1. Department of Obstetrics and GynecologyUniversity of California, Los Angeles, California, USA
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  • Daniel Y. Paik,

    1. Department of Obstetrics and GynecologyUniversity of California, Los Angeles, California, USA
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  • Andrew S. Goldstein,

    1. Department of Molecular and Medical PharmacologyUniversity of California, Los Angeles, California, USA
    2. Department of Urology, David Geffen School of MedicineUniversity of California, Los Angeles, California, USA
    3. Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell ResearchUniversity of California, Los Angeles, California, USA
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  • Owen N. Witte,

    1. The Howard Hughes Medical InstituteUniversity of California, Los Angeles, California, USA
    2. Department of Molecular and Medical PharmacologyUniversity of California, Los Angeles, California, USA
    3. Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell ResearchUniversity of California, Los Angeles, California, USA
    4. Department of Microbiology, Immunology and Molecular Genetics
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  • Artur Jaroszewicz,

    1. Department of Molecular, Cell and Developmental BiologyLos Angeles, California, USA, University of California, Los Angeles, California, USA
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  • Matteo Pellegrini,

    1. Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell ResearchUniversity of California, Los Angeles, California, USA
    2. Department of Molecular, Cell and Developmental BiologyLos Angeles, California, USA, University of California, Los Angeles, California, USA
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  • Sanaz Memarzadeh

    Corresponding author
    1. Department of Obstetrics and GynecologyUniversity of California, Los Angeles, California, USA
    2. Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell ResearchUniversity of California, Los Angeles, California, USA
    3. The VA Greater Los Angeles Health Care System, Los Angeles, California, USA
    • Department of Obstetrics and Gynecology, University of California, Los Angeles, California, USA

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    • Telephone: 310-206-1075; Fax: 310-206-3670


  • Author contributions: D.M.J.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; D.C. and A.M.S.: conception and design, collection and/or assembly of data, and data analysis and interpretation; D.Y.P. and A.G.: conception and design, and manuscript writing; A.J. and M.P.: data analysis and interpretation; O.N.W.: manuscript writing; and S.M.: collection and/or assembly of data, conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS January 22, 2013.

Abstract

Synchronous with massive shifts in reproductive hormones, the uterus and its lining the endometrium expand to accommodate a growing fetus during pregnancy. In the absence of an embryo the endometrium, composed of epithelium and stroma, undergoes numerous hormonally regulated cycles of breakdown and regeneration. The hormonally mediated regenerative capacity of the endometrium suggests that signals that govern the growth of endometrial progenitors must be regulated by estrogen and progesterone. Here, we report an antigenic profile for isolation of mouse endometrial epithelial progenitors. These cells are EpCAM+CD44+ITGA6hiThy1PECAM1PTPRCTer119, comprise a minor subpopulation of total endometrial epithelia and possess a gene expression profile that is unique and different from other cells of the endometrium. The epithelial progenitors of the endometrium could regenerate in vivo, undergo multilineage differentiation and proliferate. We show that the number of endometrial epithelial progenitors is regulated by reproductive hormones. Coadministration of estrogen and progesterone dramatically expanded the endometrial epithelial progenitor cell pool. This effect was not observed when estrogen or progesterone was administered alone. Despite the remarkable sensitivity to hormonal signals, endometrial epithelial progenitors do not express estrogen or progesterone receptors. Therefore, their hormonal regulation must be mediated through paracrine signals resulting from binding of steroid hormones to the progenitor cell niche. Discovery of signaling defects in endometrial epithelial progenitors or their niche can lead to development of better therapies in diseases of the endometrium. STEM CELLS 2013;31:808–822

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