Department of Cell and Developmental Biology, Medical School, University of Michigan, Ann Arbor, MI 48109
Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6848-6857. doi: 10.1073/pnas.1814597116. Epub 2019 Mar 14.
The endometrial epithelium of the uterus regenerates periodically. The cellular source of newly regenerated endometrial epithelia during a mouse estrous cycle or a human menstrual cycle is presently unknown. Here, I have used single-cell lineage tracing in the whole mouse uterus to demonstrate that epithelial stem cells exist in the mouse uterus. These uterine epithelial stem cells provide a resident cellular supply that fuels endometrial epithelial regeneration. They are able to survive cyclical uterine tissue loss and persistently generate all endometrial epithelial lineages, including the functionally distinct luminal and glandular epithelia, to maintain uterine cycling. The uterine epithelial stem cell population also supports the regeneration of uterine endometrial epithelium post parturition. The 5-ethynyl-2'-deoxyuridine pulse-chase experiments further reveal that this stem cell population may reside in the intersection zone between luminal and glandular epithelial compartments. This tissue distribution allows these bipotent uterine epithelial stem cells to bidirectionally differentiate to maintain homeostasis and regeneration of mouse endometrial epithelium under physiological conditions. Thus, uterine function over the reproductive lifespan of a mouse relies on stem cell-maintained rhythmic endometrial regeneration.
子宫的子宫内膜周期性地再生。目前尚不清楚在小鼠动情周期或人类月经周期中，新再生的子宫内膜上皮的细胞来源。在这里，我使用单细胞谱系追踪整个小鼠子宫，证明了小鼠子宫中存在上皮干细胞。这些子宫上皮干细胞提供了一个常驻的细胞供应，为子宫内膜上皮的再生提供燃料。它们能够在周期性的子宫组织损失中存活，并持续产生所有的子宫内膜上皮谱系，包括功能不同的腔上皮和腺上皮，以维持子宫周期。子宫上皮干细胞群还支持产后子宫子宫内膜上皮的再生。5-乙炔基-2'-脱氧尿苷脉冲追踪实验进一步表明，这个干细胞群体可能位于腔上皮和腺上皮隔室之间的交界区。这种组织分布使这些双能子宫上皮干细胞能够双向分化，在生理条件下维持小鼠子宫内膜上皮的稳态和再生。因此，小鼠生殖寿命内的子宫功能依赖于干细胞维持的有节奏的子宫内膜再生。
