title: The mouse endometrium contains epithelial, endothelial and leucocyte populations expressing the stem cell marker telomerase reverse transcriptase.
abstract: OBJECTIVE
  The mouse endometrium harbours stem/progenitor cells that express the stem cell marker mouse telomerase reverse transcriptase (mTert).
  
  
  RESULTS
  We used a mouse carrying a transgenic reporter for mTert promoter activity to identify rare endometrial populations of epithelial and endothelial cells that express mTert.
  
  
  BACKGROUND
  Stem/progenitor cells are hypothesized to be responsible for the remarkable regenerative capacity of the endometrium, but the lack of convenient endometrial stem/progenitor markers in the mouse has hampered investigations into the identity of these cells.
  
  
  METHODS
  A mouse containing a green fluorescent protein (GFP) reporter under the control of the telomerase reverse transcriptase promoter (mTert-GFP) was used to identify potential stem/progenitor cells in the endometrium. mTert promoter activity was determined using fluorescence microscopy and flow cytometry to identify GFP(+) cells. GFP(+) cells were examined for epithelial, stromal, endothelial, leucocyte and proliferation markers and bromodeoxyuridine retention to determine their identity. The endometrium of ovariectomized mice was compared to that of intact cycling mice to establish the role of ovarian hormones in maintaining mTert-expressing cells.
  
  
  RESULTS
  We found that mTert-GFP is expressed by rare luminal and glandular epithelial cells (0.3% of epithelial cells by flow cytometry), rare CD45(-) cells in the stromal compartment (0.028 ± 0.010% of stromal cells by microscopy) and many CD45(+) leucocytes. Ovariectomy resulted in significant decrease of mTert-GFP(+) epithelial cells (P = 0.029 for luminal epithelium; P = 0.034 for glandular epithelium) and a decrease in the percentage of mTert-GFP(+) CD45(+) leucocytes in the stromal compartment (P = 0.015). However, CD45(-) mTert-GFP(+) cells in the stromal compartment were maintained in ovariectomized mice. This population is enriched for cells bearing the endothelial marker CD31 (10.3% of CD90(-) CD45(-) and 97.8% CD90(+) CD45(-) by flow cytometry). CD45(-) mTert-GFP(+) cells also immunostained for the endothelial marker von Willebrand factor. These results suggest that the endometrial epithelium and vasculature are foci of stem/progenitor activity and provide a system to investigate molecular mechanisms involved in endometrial regeneration and repair.
  
  
  CONCLUSIONS
  The stem/progenitor activity of endometrial mTert-GFP(+) cells needs to be experimentally verified.
  
  
  CONCLUSIONS
  The identification and characterization of mTert-expressing progenitor cells in the mouse will facilitate the identification of equivalent populations in the human endometrium that are likely to be involved in endometrial function, fertility and disease.
  
  
  METHODS
  Not applicable.
  
  
  BACKGROUND
  This study was funded by National Health and Medical Research Council (NHMRC) of Australia grants (1085435, C.E.G., J.A.D.), 1021127 (C.E.G.), NHMRC Senior Research Fellowship (1042298, C.E.G.), the Victorian Infrastructure Support Program, U.S. National Institutes of Health grant R01 DK084056 (D.T.B.) and the Harvard Stem Cell Institute (D.T.B.). The authors have no conflicts of interest to declare.
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, 27-31 Wright St., Clayton, Victoria, Australia Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia james.deane@hudson.org.au caroline.gargett@hudson.org.au.
authors.forename: James A
authors.initials: JA
authors.lastname: Deane
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, 27-31 Wright St., Clayton, Victoria, Australia.
authors.forename: Y Rue
authors.initials: YR
authors.lastname: Ong
authors.affiliation: Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Cain
authors.affiliation: Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: W Samantha N
authors.initials: WS
authors.lastname: Jayasekara
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, 27-31 Wright St., Clayton, Victoria, Australia.
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Tiwari
authors.affiliation: Boston Children's Hospital, Harvard Medical School/Harvard Stem Cell Institute, Boston, MA, USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Carlone
authors.affiliation: Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia Present address: The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia Present address: UNSW Faculty of Medicine, St Vincent's Clinical School, St Vincent's Hospital, Randwick, New South Wales, Australia.
authors.forename: D Neil
authors.initials: DN
authors.lastname: Watkins
authors.affiliation: Boston Children's Hospital, Harvard Medical School/Harvard Stem Cell Institute, Boston, MA, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Breault
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, 27-31 Wright St., Clayton, Victoria, Australia Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia james.deane@hudson.org.au caroline.gargett@hudson.org.au.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Gargett
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D010052:Ovariectomy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D049452:Green Fluorescent Proteins; D019098:Telomerase; C509187:Tert protein, mouse; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse
keywords: endometrium; endothelial; epithelial; leucocyte; mesenchymal stem cell; ovariectomy; progenitor; regeneration; stromal; telomerase