Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro.
Authors
Garcia-Alonso, Luz
Handfield, Louis-François
Fernando, Ridma C
Gardner, Lucy
Hoo, Regina
Sancho-Serra, Carmen
Kwakwa, Kwasi
Tuck, Elizabeth
Lorenzi, Valentina
Massalha, Hassan
Prete, Martin
Kleshchevnikov, Vitalii
Tarkowska, Aleksandra
Porter, Tarryn
Mazzeo, Cecilia Icoresi
van Dongen, Stijn
Dabrowska, Monika
Park, Jong-Eun
Jimenez-Linan, Mercedes
Campos, Lia
Kiselev, Vladimir Yu
Lindskog, Cecilia
Ayuk, Paul
Prigmore, Elena
Turco, Margherita Y
Publication Date
2021-12Journal Title
Nat Genet
ISSN
1061-4036
Publisher
Springer Science and Business Media LLC
Volume
53
Issue
12
Pages
1698-1711
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Garcia-Alonso, L., Handfield, L., Roberts, K., Nikolakopoulou, K., Fernando, R. C., Gardner, L., Woodhams, B., et al. (2021). Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro.. Nat Genet, 53 (12), 1698-1711. https://doi.org/10.1038/s41588-021-00972-2
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
Article, /631/80, /631/45, article
Sponsorship
Wellcome Trust (200841/Z/16/Z)
Identifiers
s41588-021-00972-2, 972
External DOI: https://doi.org/10.1038/s41588-021-00972-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/331800
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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