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Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
- Source :
- Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
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. Single-cell and spatial transcriptomic profiling of the human endometrium highlights pathways governing the proliferative and secretory phases of the menstrual cycle. Analyses of endometrial organoids show that WNT and NOTCH signaling modulate differentiation into the secretory and ciliated epithelial lineages, respectively. Correction in: Nature Genetics, 55, page 165 (2023)DOI: 10.1038/s41588-022-01287-6
- Subjects :
- 631/45
Cell type
Notch signaling pathway
Reproduktionsmedicin och gynekologi
In Vitro Techniques
Cell fate determination
Biology
Endometrium
Tissue Culture Techniques
Transcriptome
Spatio-Temporal Analysis
Downregulation and upregulation
Obstetrics, Gynecology and Reproductive Medicine
Genetics
Organoid
medicine
Humans
Cell Lineage
Gonadal Steroid Hormones
Menstrual Cycle
Receptors, Notch
Uterus
article
Wnt signaling pathway
Cell Differentiation
Endometrial Neoplasms
Cell biology
Organoids
Wnt Proteins
medicine.anatomical_structure
Cellular Microenvironment
Female
631/80
Signal Transduction
Subjects
Details
- ISSN :
- 15461718 and 10614036
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....f8a61416308e9fc300a6b5852263e494