Identification of label-retaining cells in mouse endometrium.
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 (LRC) approach. We hypothesized that mouse endometrium contains small populations of both epithelial and stromal somatic stem/progenitor cells that 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 to identify their niche in this highly regenerative tissue. Endometrium was labeled for 3 days with bromodeoxyuridine (BrdU) in postnatal day 3 (P3) mice 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-alpha (ER-alpha). 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 stem cell antigen-1, CD45(-), and some (16%) expressed ER-alpha, indicating their capacity to respond to estrogen and transmit paracrine signals to epithelial cells for endometrial epithelium regeneration. Both epithelial LRCs and some stromal LRCs, mainly located at the endometrial-myometrial junction, were recruited into the 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 stem-like cells may be responsible for endometrial regeneration.
Chan
Rachel W S
RW
Centre for Women's Health Research, Monash University Department of Obstetrics and Gynaecology, Monash Medical Centre, Clayton, VIC, Australia.
Gargett
Caroline E
CE
D000199:Actins / Q000378:metabolism; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D045166:Estradiol Congeners / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000199:Actins; D000067696:Ataxin-1; D000067528:Ataxins; D001973:Bromodeoxyuridine; D045166:Estradiol Congeners; D047628:Estrogen Receptor alpha; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C000593749:ATXN1 protein, human; C000593750:Atxn1 protein, mouse; C000593751:Atxn1 protein, rat; C498862:Acta2 protein, rat