Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
Luz Garcia-Alonso, Louis-François Handfield, Kenny Roberts, Konstantina Nikolakopoulou, Ridma C. Fernando, Lucy Gardner, Benjamin Woodhams, Anna Arutyunyan, Krzysztof Polanski, Regina Hoo, Carmen Sancho-Serra, Tong Li, Kwasi Kwakwa, Elizabeth Tuck, Valentina Lorenzi, Hassan Massalha, Martin Prete, Vitalii Kleshchevnikov, Aleksandra Tarkowska, Tarryn Porter, Cecilia Icoresi Mazzeo, Stijn van Dongen, Monika Dabrowska, Vasyl Vaskivskyi, Krishnaa T. Mahbubani, Jong-eun Park, Mercedes Jimenez-Linan, Lia Campos, Vladimir Yu. Kiselev, Cecilia Lindskog, Paul Ayuk, Elena Prigmore, Michael R. Stratton, Kourosh Saeb-Parsy, Ashley Moffett, Luiza Moore, Omer A. Bayraktar, Sarah A. Teichmann, Margherita Y. Turco, Roser Vento-Tormo
Abstract
The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma.
Datasets
1. Non-pregnant Uterus (Endometrium - All)
2. Non-pregnant Uterus (Endometrium - Organoid)
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Source data
https://cellxgene.cziscience.com/collections/32f2fd23-ec74-486f-9544-e5b2f41725f5
Alias names
EGAD00001007909, E-MTAB-10287, E-MTAB-9260, E-MTAB-10283, PMID34857954, PMC8648563
Cite this study
Garcia-Alonso, L., Handfield, L.F., Roberts, K., Nikolakopoulou, K., Fernando, R.C., Gardner, L., Woodhams, B., Arutyunyan, A., Polanski, K., Hoo, R. and Sancho-Serra, C., 2021. Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro. Nature genetics, 53(12), pp.1698-1711. https://doi.org/10.1038/s41588-021-00972-2