School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, 2308 NSW, Australia; Hunter Medical Research Institute, New Lambton Heights, 2305 NSW, Australia.
Genomic and Epigenetics Group, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, 2010 NSW, Australia.
Cell Rep. 2020 Feb 4;30(5):1463-1477.e7. doi: 10.1016/j.celrep.2020.01.003.
The intact vaginal epithelium is essential for women's reproductive health and provides protection against HIV and sexually transmitted infections. How this epithelium maintains itself remains poorly understood. Here, we used single-cell RNA sequencing (RNA-seq) to define the diverse cell populations in the vaginal epithelium. We show that vaginal epithelial cell proliferation is limited to the basal compartment without any obvious label-retaining cells. Furthermore, we developed vaginal organoids and show that the basal cells have increased organoid forming efficiency. Importantly, Axin2 marks a self-renewing subpopulation of basal cells that gives rise to differentiated cells over time. These cells are ovariectomy-resistant stem cells as they proliferate even in the absence of hormones. Upon hormone supplementation, these cells expand and reconstitute the entire vaginal epithelium. Wnt/β-catenin is essential for the proliferation and differentiation of vaginal stem cells. Together, these data define heterogeneity in vaginal epithelium and identify vaginal epithelial stem cells.
完整的阴道上皮对于女性的生殖健康至关重要，它能提供针对 HIV 和性传播感染的保护。然而，阴道上皮如何维持自身稳定的机制仍不清楚。在这里，我们利用单细胞 RNA 测序（RNA-seq）来鉴定阴道上皮中的多种细胞群体。我们发现阴道上皮细胞的增殖仅限于基底细胞层，不存在明显的标记保留细胞。此外，我们还开发了阴道类器官，并表明基底细胞具有更高的类器官形成效率。重要的是，Axin2 标记了一个具有自我更新能力的基底细胞亚群，该亚群能够随着时间的推移产生分化细胞。这些细胞是卵巢切除抵抗性的干细胞，因为它们即使在没有激素的情况下也会增殖。在激素补充后，这些细胞会扩增并重新构建整个阴道上皮。Wnt/β-catenin 对于阴道干细胞的增殖和分化至关重要。这些数据共同定义了阴道上皮的异质性，并鉴定出了阴道上皮干细胞。
