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

Luz García‐Alonso; Louis‐François Handfield; Kenny Roberts; Κωνσταντίνα Νικολακοπούλου; Ridma C. Fernando; Lucy Gardner; Benjamin Woodhams; Anna Arutyunyan; Krzysztof Polański; Regina Hoo; Carmen Sancho‐Serra; Tong Li; Kwasi Kwakwa; Elizabeth J. Tuck; Valentina Lorenzi; Hassan Massalha; Martin Prete; Vitalii Kleshchevnikov; Aleksandra Tarkowska; Tarryn Porter; Cecilia Icoresi-Mazzeo; Stijn van Dongen; Monika H. Dabrowska; Vasyl Vaskivskyi; Krishnaa T. A. Mahbubani; Jong-eun Park; Mercedes Jimenez‐Liñan; Lia S. Campos; Vladimir Yu Kiselev; Cecilia Lindskog

doi:10.1038/s41588-021-00972-2

GenomicsNature GeneticsDec 1, 2021

Peer-reviewed journal article

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

Luz García‐Alonso iD, Louis‐François Handfield, Kenny Roberts iD, Κωνσταντίνα Νικολακοπούλου iD, Ridma C. Fernando, Lucy Gardner iD, Benjamin Woodhams iD, Anna Arutyunyan iD, Krzysztof Polański iD, Regina Hoo iD, Carmen Sancho‐Serra iD, Tong Li iD, Kwasi Kwakwa, Elizabeth J. Tuck iD, Valentina Lorenzi iD, Hassan Massalha iD, Martin Prete iD, Vitalii Kleshchevnikov iD, Aleksandra Tarkowska iD, Tarryn Porter iD, Cecilia Icoresi-Mazzeo iD, Stijn van Dongen iD, Monika H. Dabrowska, Vasyl Vaskivskyi iD, Krishnaa T. A. Mahbubani iD, , Roser Vento‐Tormo iD

Abstract

The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated single-cell and spatial reference maps of the human uterus and 3D endometrial organoid cultures. We dissect the signalling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids highlights common pathways regulating the differentiation of secretory and ciliated lineage in vivo and in vitro. We show in vitro that downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. These mechanistic insights provide a platform for future development of treatments for a range of common endometrial disorders including endometriosis and carcinoma.

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