Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
Open Access
- 2 December 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 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
This publication has 64 references indexed in Scilit:
- Integrated genomic characterization of endometrial carcinomaNature, 2013
- Lgr5+ve Stem/Progenitor Cells Contribute to Nephron Formation during Kidney DevelopmentCell Reports, 2012
- The evolution of menstruation: A new model for genetic assimilationBioEssays, 2011
- Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failureNature Medicine, 2011
- Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In VitroCell Stem Cell, 2010
- Progesterone Inhibition of Wnt/β-Catenin Signaling in Normal Endometrium and Endometrial CancerClinical Cancer Research, 2009
- A role for menstruation in preconditioning the uterus for successful pregnancyAmerican Journal of Obstetrics and Gynecology, 2009
- Lgr5 marks cycling, yet long-lived, hair follicle stem cellsNature Genetics, 2008
- The evolution of human reproduction: A primatological perspectiveAmerican Journal of Physical Anthropology, 2007
- Dickkopf-1, an Inhibitor of Wnt Signaling, Is Regulated by Progesterone in Human Endometrial Stromal CellsJournal of Clinical Endocrinology & Metabolism, 2006