Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro.
Cell Differentiation
Cell Lineage
Cellular Microenvironment
Endometrial Neoplasms
/ pathology
Endometrium
/ embryology
Female
Gonadal Steroid Hormones
/ metabolism
Humans
In Vitro Techniques
Menstrual Cycle
Organoids
Receptors, Notch
/ metabolism
Signal Transduction
Spatio-Temporal Analysis
Tissue Culture Techniques
Transcriptome
Uterus
/ pathology
Wnt Proteins
/ metabolism
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
13
02
2021
accepted:
18
10
2021
pubmed:
4
12
2021
medline:
29
12
2021
entrez:
3
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34857954
doi: 10.1038/s41588-021-00972-2
pii: 10.1038/s41588-021-00972-2
pmc: PMC8648563
doi:
Substances chimiques
Gonadal Steroid Hormones
0
Receptors, Notch
0
Wnt Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1698-1711Subventions
Organisme : Wellcome Trust (Wellcome)
ID : 200841/Z/16/Z
Organisme : Wellcome Trust (Wellcome)
ID : 211276/Z/18/Z
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S036350/1
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : WT206194
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
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