Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.
Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.
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DOI：
10.1038/ncb3516
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发表时间：
2017-05
影响因子：
21.3
通讯作者：
Burton GJ
中科院分区：
文献类型：
--
作者：
Turco MY;Gardner L;Hughes J;Cindrova-Davies T;Gomez MJ;Farrell L;Hollinshead M;Marsh SGE;Brosens JJ;Critchley HO;Simons BD;Hemberger M;Koo BK;Moffett A;Burton GJ
在人类，子宫内膜，即子宫黏膜衬里，在整个月经周期和怀孕期间都会经历动态变化。尽管子宫内膜作为着床部位和对胚胎的营养支持很重要，但目前还没有一种长期的培养系统来概括体外子宫内膜的功能。我们调整了用于建立人类成年干细胞来源的有机类细胞培养的条件，以产生正常和蜕膜的人类子宫内膜的3D培养。这些有机物质长期扩张，遗传稳定，在生殖激素治疗后分化。子宫内膜和蜕膜中的单个细胞都可以产生一个功能齐全的类器官。转录分析证实，有机物质与原始起源组织有很大的相似性。在暴露于妊娠信号的情况下，子宫内膜器质形成早期妊娠的特征。我们还从恶性子宫内膜中提取了有机化合物，为研究常见疾病，如子宫内膜异位症和子宫内膜癌，以及早期妊娠的生理提供了基础。
In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem cell-derived organoid cultures to generate 3D cultures of normal and decidualised human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.