Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria.
Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.
Endocrinology. 2019 Oct 1;160(10):2282-2297. doi: 10.1210/en.2019-00314.
The human endometrium is the inner lining of the uterus consisting of stromal and epithelial (secretory and ciliated) cells. It undergoes a hormonally regulated monthly cycle of growth, differentiation, and desquamation. However, how these cyclic changes control the balance between secretory and ciliated cells remains unclear. Here, we established endometrial organoids to investigate the estrogen (E2)-driven control of cell fate decisions in human endometrial epithelium. We demonstrate that they preserve the structure, expression patterns, secretory properties, and E2 responsiveness of their tissue of origin. Next, we show that the induction of ciliated cells is orchestrated by the coordinated action of E2 and NOTCH signaling. Although E2 is the primary driver, inhibition of NOTCH signaling provides a permissive environment. However, inhibition of NOTCH alone is not sufficient to trigger ciliogenesis. Overall, we provide insights into endometrial biology and propose endometrial organoids as a robust and powerful model for studying ciliogenesis in vitro.
人类子宫内膜是子宫的内层组织，由基质和上皮（分泌细胞和纤毛细胞）细胞组成。它经历一个受激素调节的周期性生长、分化和脱落过程。然而，这些周期性变化如何控制分泌细胞和纤毛细胞之间的平衡仍不清楚。在这里，我们建立了子宫内膜类器官，以研究雌激素（E2）如何驱动人类子宫内膜上皮细胞命运的决定。我们证明它们保留了其组织来源的结构、表达模式、分泌特性和对 E2 的反应性。接下来，我们表明纤毛细胞的诱导是由 E2 和 NOTCH 信号的协调作用来协调的。虽然 E2 是主要的驱动因素，但 NOTCH 信号的抑制提供了一个许可的环境。然而，单独抑制 NOTCH 信号不足以引发纤毛发生。总的来说，我们提供了对子宫内膜生物学的深入了解，并提出子宫内膜类器官是研究体外纤毛发生的强大模型。
