1. Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
- Author
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Elena Prigmore, Louis-François Handfield, Michael R. Stratton, Tong Li, Mercedes Jimenez-Linan, Lucy Gardner, Luz Garcia-Alonso, Tarryn Porter, Krishnaa T. Mahbubani, Vitalii Kleshchevnikov, Anna Arutyunyan, Hassan Massalha, Monika Dabrowska, Paul Ayuk, Kwasi Kwakwa, Ashley Moffett, Benjamin Woodhams, Kourosh Saeb-Parsy, Ridma C. Fernando, Regina Hoo, Elizabeth Tuck, Konstantina Nikolakopoulou, Stijn van Dongen, Valentina Lorenzi, Jong-Eun Park, Kenny Roberts, Cecilia Icoresi Mazzeo, Margherita Y. Turco, Vasyl Vaskivskyi, Martin Prete, Aleksandra Tarkowska, Roser Vento-Tormo, Krzysztof Polanski, Carmen Sancho-Serra, Cecilia Lindskog, Omer Ali Bayraktar, Vladimir Yu. Kiselev, Sarah A. Teichmann, Lia S. Campos, Luiza Moore, Roberts, Kenny [0000-0001-6155-0821], Nikolakopoulou, Konstantina [0000-0003-2306-590X], Woodhams, Benjamin [0000-0003-2801-5733], Arutyunyan, Anna [0000-0003-0453-5443], Polanski, Krzysztof [0000-0002-2586-9576], Li, Tong [0000-0002-8240-4476], Vaskivskyi, Vasyl [0000-0002-4080-4965], Mahbubani, Krishnaa T. [0000-0002-1327-2334], Stratton, Michael R. [0000-0001-6035-153X], Saeb-Parsy, Kourosh [0000-0002-0633-3696], Moffett, Ashley [0000-0002-8388-9073], Moore, Luiza [0000-0001-5315-516X], Bayraktar, Omer A. [0000-0001-6055-277X], Teichmann, Sarah A. [0000-0002-6294-6366], Vento-Tormo, Roser [0000-0002-9870-8474], Apollo - University of Cambridge Repository, Mahbubani, Krishnaa T [0000-0002-1327-2334], Stratton, Michael R [0000-0001-6035-153X], Bayraktar, Omer A [0000-0001-6055-277X], Teichmann, Sarah A [0000-0002-6294-6366], Mahbubani, Krishnaa [0000-0002-1327-2334], and Teichmann, Sarah [0000-0002-6294-6366]
- Subjects
631/45 ,Cell type ,Notch signaling pathway ,Reproduktionsmedicin och gynekologi ,In Vitro Techniques ,Cell fate determination ,Biology ,Endometrium ,Tissue Culture Techniques ,Transcriptome ,Spatio-Temporal Analysis ,Downregulation and upregulation ,Obstetrics, Gynecology and Reproductive Medicine ,Genetics ,Organoid ,medicine ,Humans ,Cell Lineage ,Gonadal Steroid Hormones ,Menstrual Cycle ,Receptors, Notch ,Uterus ,article ,Wnt signaling pathway ,Cell Differentiation ,Endometrial Neoplasms ,Cell biology ,Organoids ,Wnt Proteins ,medicine.anatomical_structure ,Cellular Microenvironment ,Female ,631/80 ,Signal Transduction - 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. Single-cell and spatial transcriptomic profiling of the human endometrium highlights pathways governing the proliferative and secretory phases of the menstrual cycle. Analyses of endometrial organoids show that WNT and NOTCH signaling modulate differentiation into the secretory and ciliated epithelial lineages, respectively. Correction in: Nature Genetics, 55, page 165 (2023)DOI: 10.1038/s41588-022-01287-6
- Published
- 2021