title: Identification of quiescent, stem-like cells in the distal female reproductive tract.
abstract: In fertile women, the endometrium undergoes regular cycles of tissue build-up and regression. It is likely that uterine stem cells are involved in this remarkable turn over. The main goal of our current investigations was to identify slow-cycling (quiescent) endometrial stem cells by means of a pulse-chase approach to selectively earmark, prospectively isolate, and characterize label-retaining cells (LRCs). To this aim, transgenic mice expressing histone2B-GFP (H2B-GFP) in a Tet-inducible fashion were administered doxycycline (pulse) which was thereafter withdrawn from the drinking water (chase). Over time, dividing cells progressively loose GFP signal whereas infrequently dividing cells retain H2B-GFP expression. We evaluated H2B-GFP retaining cells at different chase time points and identified long-term (LT; >12 weeks) LRCs. The LT-LRCs are negative for estrogen receptor-α and express low levels of progesterone receptors. LRCs sorted by FACS are able to form spheroids capable of self-renewal and differentiation. Upon serum stimulation spheroid cells are induced to differentiate and form glandular structures which express markers of mature műllerian epithelial cells. Overall, the results indicate that quiescent cells located in the distal oviduct have stem-like properties and can differentiate into distinct cell lineages specific of endometrium, proximal and distal oviduct. Future lineage-tracing studies will elucidate the role played by these cells in homeostasis, tissue injury and cancer of the female reproductive tract in the mouse and eventually in man.
authors: Department of Obstetrics & Gynecology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands.
authors: Yongyi
authors: Y
authors: Wang
authors: Andrea
authors: A
authors: Sacchetti
authors: Matthijs R
authors: MR
authors: van Dijk
authors: Marten
authors: M
authors: van der Zee
authors: Paul H
authors: PH
authors: van der Horst
authors: Rosalie
authors: R
authors: Joosten
authors: Curt W
authors: CW
authors: Burger
authors: J Anton
authors: JA
authors: Grootegoed
authors: Leen J
authors: LJ
authors: Blok
authors: Riccardo
authors: R
authors: Fodde
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010057:Oviducts / Q000166:cytology* / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*