1. Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
- Author
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Luz Garcia-Alonso, Ridma C. Fernando, Regina Hoo, Kenny Roberts, Vasyl Vaskivskyi, Vitalii Kleshchevnikov, Aleksandra Tarkowska, Anna Arutyunyan, Jong-Eun Park, Roser Vento-Tormo, Cecilia Icoresi Mazzeo, Tong Li, Tarryn Porter, Kourosh Saeb-Parsy, Paul Ayuk, Michael R. Stratton, Monika Dabrowska, Ashley Moffett, Louis-François Handfield, Elena Prigmore, Ben Woodhams, Stijn van Dongen, Elizabeth Tuck, Krishna T. Mahbubani, Mercedes Jimenez-Linan, Lucy Gardner, Konstantina Nikolakopoulou, Kwasi Kwakwa, Margherita Y. Turco, Krzysztof Polanski, Omer Ali Bayraktar, Vladimir Yu. Kiselev, Carmen Sancho-Serra, Cecilia Lindskog, Sarah A. Teichmann, Lia S. Campos, and Luiza Moore
- Subjects
medicine.anatomical_structure ,Downregulation and upregulation ,In vivo ,Wnt signaling pathway ,medicine ,Uterus ,Organoid ,Endometriosis ,Cell fate determination ,Biology ,Endometrium ,medicine.disease ,Cell biology - Abstract
The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated single-cell and spatial reference maps of the human uterus and 3D endometrial organoid cultures. We dissect the signalling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids highlights common pathways regulating the differentiation of secretory and ciliated lineage in vivo and in vitro. We show in vitro that downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. These mechanistic insights provide a platform for future development of treatments for a range of common endometrial disorders including endometriosis and carcinoma.
- Published
- 2021