Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability
Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability
复制标题
DOI：
10.1242/dev.148478
复制
发表时间：
2017-05-15
期刊：
影响因子：
4.6
通讯作者：
Vankelecom, Hugo
中科院分区：
文献类型：
--
作者：
Boretto, Matteo;Cox, Benoit;Vankelecom, Hugo
子宫内膜对生殖至关重要，它会经历动态的周期性组织重塑。对其分子和细胞调控的了解甚少，这主要是由于缺乏研究模型。在此，我们从小鼠和人子宫内膜建立了一种新颖且有前景的类器官模型。在WNT激活条件下，将解离的子宫内膜组织包埋在基质胶中，迅速形成了类器官结构，这些结构显示出长期的扩增能力，并重现了组织上皮的分子和组织学表型。补充的WNT水平决定了所获得的小鼠子宫内膜类器官的类型：高WNT产生的囊性类器官比低WNT下获得的致密类器官表现出更分化的表型。这些类器官模拟了子宫内膜上皮对激素的生理反应，包括在雌激素作用下细胞增殖增加以及在孕激素作用下成熟。此外，人子宫内膜类器官在激素处理下在形态 - 组织学和分子水平上都重现了月经周期。总之，我们建立了一个子宫内膜类器官培养系统，重现了组织上皮生理并允许长期扩增。这种新模型为研究这个关键生殖器官的生物学及病理学潜在机制提供了一个强有力的工具。
The endometrium, which is of crucial importance for reproduction, undergoes dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular regulation is poor, primarily owing to a lack of study models. Here, we have established a novel and promising organoid model from both mouse and human endometrium. Dissociated endometrial tissue, embedded in Matrigel under WNT-activating conditions, swiftly formed organoid structures that showed long-term expansion capacity, and reproduced the molecular and histological phenotype of the tissue's epithelium. The supplemented WNT level determined the type of mouse endometrial organoids obtained: high WNT yielded cystic organoids displaying a more differentiated phenotype than the dense organoids obtained in low WNT. The organoids phenocopied physiological responses of endometrial epithelium to hormones, including increased cell proliferation under estrogen and maturation upon progesterone. Moreover, the human endometrial organoids replicated the menstrual cycle under hormonal treatment at both the morpho-histological and molecular levels. Together, we established an organoid culture system for endometrium, reproducing tissue epithelium physiology and allowing long-term expansion. This novel model provides a powerful tool for studying mechanisms underlying the biology as well as the pathology of this key reproductive organ.