Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro.
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IF: 41.307
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Cited by: 177
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Datasets
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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.

Keywords

Seurat
RNAscope
Spatial Transcriptomics
smFISH

MeSH terms

Cell Differentiation
Cell Lineage
Cellular Microenvironment
Endometrial Neoplasms
Endometrium
Female
Gonadal Steroid Hormones
Humans
In Vitro Techniques
Menstrual Cycle
Organoids
Receptors, Notch
Signal Transduction
Spatio-Temporal Analysis
Tissue Culture Techniques
Transcriptome
Uterus
Wnt Proteins

Authors

Garcia-Alonso, Luz
Handfield, Louis-François
Roberts, Kenny
Nikolakopoulou, Konstantina
Fernando, Ridma C
Gardner, Lucy
Woodhams, Benjamin
Arutyunyan, Anna
Polanski, Krzysztof
Hoo, Regina
Sancho-Serra, Carmen
Li, Tong
Kwakwa, Kwasi
Tuck, Elizabeth
Lorenzi, Valentina
Massalha, Hassan
Prete, Martin
Kleshchevnikov, Vitalii
Tarkowska, Aleksandra
Porter, Tarryn
Mazzeo, Cecilia Icoresi
van Dongen, Stijn
Dabrowska, Monika
Vaskivskyi, Vasyl
Mahbubani, Krishnaa T
Park, Jong-Eun
Jimenez-Linan, Mercedes
Campos, Lia
Kiselev, Vladimir Yu
Lindskog, Cecilia
Ayuk, Paul
Prigmore, Elena
Stratton, Michael R
Saeb-Parsy, Kourosh
Moffett, Ashley
Moore, Luiza
Bayraktar, Omer A
Teichmann, Sarah A
Turco, Margherita Y
Vento-Tormo, Roser

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