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Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro.

Published version
Peer-reviewed

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Authors

Garcia-Alonso, Luz 
Handfield, Louis-François 
Nikolakopoulou, Konstantina  ORCID logo  https://orcid.org/0000-0003-2306-590X
Fernando, Ridma C 

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.

Description

Keywords

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

Journal Title

Nat Genet

Conference Name

Journal ISSN

1061-4036
1546-1718

Volume Title

53

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (200841/Z/16/Z)
European Commission Horizon 2020 (H2020) ERC (853546)