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Tissue-Specific Stem Cells |
1 Centre for Women's Health Research, Monash Institute of Medical Research and Monash University Department of Obstetrics and Gynecology, Monash Medical Centre, Clayton Victoria, Australia
* To whom correspondence should be addressed. E-mail: caroline.gargett{at}med.monash.edu.au.
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Abstract |
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Human and mouse endometrium (lining of the uterus) undergo cycles of growth and regression as part of each reproductive cycle. A well-known method to identify somatic stem/progenitor cells and their location in the stem cell niche is the label retaining cell approach (LRC). We hypothesized that mouse endometrium contains small populations of both epithelial and stromal somatic stem/progenitor cells which may be detected by the LRC technique. The overall objective of this study was to identify and quantify LRCs in mouse endometrium, to determine their location and identify their niche in this highly regenerative tissue. Endometrium was labeled for 3 days with bromodeoxyuridine (BrdU) in postnatal (P3) prior to gland development and prepubertal (P19) mice after glands had formed, followed by chase periods of up to 12 weeks. After an 8-week chase, 3% of epithelial nuclei immunostained with BrdU antibody and were considered epithelial LRCs. These were primarily located in the luminal epithelium. Epithelial LRCs did not express estrogen receptor-
(ER-). Stromal LRCs (6%) were found adjacent to luminal epithelium, at the endometrial-myometrial junction and near blood vessels after a 12-week chase. Stromal LRCs were Sca-1-, CD45-, and some (16%) expressed ER-, indicating their capacity to respond to estrogen and transmit paracrine signals to epithelial cells for endometrial epithelium regeneration. Both epithelial LRC and some stromal LRCs mainly located at the endometrial-myometrial junction were recruited into cell cycle after estrogen-stimulated endometrial regeneration, indicating a functional response to proliferative signals. This study has demonstrated for the first time the presence of both epithelial and stromal LRCs in mouse endometrium suggesting that these stemlike cells may be responsible for endometrial regeneration.
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