Oral Presentation ESA-SRB Conference 2015

Expression of the Stem Cell Marker mTert Identifies Epithelial, Endothelial and Leukocyte populations in the Mouse Endometrium. (#30)

James A Deane 1 , Y Rue Ong 1 , David T Breault 2 , Caroline E Gargett 1
  1. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia
  2. Division of Endocrinology, Children's Hospital , Harvard Medical School, Boston, MA, USA

Stem/progenitor cells are thought to be responsible for the regenerative capacity of the endometrium. However the role of these cells has been difficult to investigate in mouse models due to the lack of a marker for easy identification and tracking. Mouse telomerase reverse transcriptase (mTert) is the rate limiting component of the telomerase complex that stem cells use to escape senescence, and a stem cell marker in bone marrow and intestine. We have used transgenic mice with reporter constructs for mTert to identify and characterize putative endometrial stem/progenitor cells. Endometrial mTert expression was examined by microscopy and flow cytometry in mice expressing GFP under the control of the mTert promoter (mTert-GFP). The fate of endometrial mTert cells was examined in mice featuring inducible permanent mTert-Cre-mediated expression of tdTomato in the mTert lineage (mTert-CreER::R26R-tdTomato). CD45+ leukocytes were the most abundant mTert-GFP cell type and are likely to account for the majority of telomerase activity in the endometrium. The abundance of mTert-GFP leukocytes was decreased by ovariectomy, indicating that their recruitment/maintenance is promoted by ovarian hormones. mTert-GFP leukocytes are likely to be a transient bone marrow-derived population rather than endometrial stem/progenitor cells. Rare populations of intrinsic (CD45neg) mTert-GFP were detected in the endometrium and , unlike CD45+ leukocytes, the relative percentage of CD45neg mTert-GFP cells did not decrease in ovariectomised mice, indicating their presence is independent of ovarian hormones. This is in keeping with the concept of endometrial progenitor populations that survive hormonal deprivation. The CD45neg mTert-GFP population included cells expressing epithelial (EpCAM) and endothelial (CD31, von Willebrand factor) markers. Lineage tracing using the mTert-CreER::R26R-tdTomato mouse showed mTert expressing cells contribute to epithelial and leukocyte lineages in the endometrium. Our results provide evidence that mTert-expressing cells are involved in replenishing and regenerating epithelial and endothelial structures of the endometrium.