Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium
Nature Cell Biology
Nature Publishing Group
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Turco, M., Gardner, L., Hughes, J., Cindrova-Davies, T., Gomez, M., Farrell, L., Hollinshead, M., et al. (2017). Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nature Cell Biology, 19 568-577. https://doi.org/10.1038/ncb3516
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 three-dimensional cultures of normal and decidualized 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.
disease model, homeostasis, organogenesis, stem-cell differentiation
This work was supported by the Medical Research Council (MR/L020041/1), the Centre for Trophoblast Research, University of Cambridge and the Wellcome Trust (RG60992). M.Y.T. has received funding from the E.U. 7th Framework Programme for research, technological development and demonstration under grant agreement no PIEF-GA-2013-629785. J.H. was supported by a Wellcome Trust vacation scholarship. B.-K.K. is supported by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (101241/Z/13/Z) and receives a core support grant from the Wellcome Trust and MRC to the WT-MRC Cambridge Stem Cell Institute.
European Commission (629785)
Wellcome Trust (101241/Z/13/Z)
External DOI: https://doi.org/10.1038/ncb3516
This record's URL: https://www.repository.cam.ac.uk/handle/1810/264553