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

© 2021. The Author(s)..

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.

Errataetall:

CommentIn: Nat Genet. 2021 Dec;53(12):1628-1630. - PMID 34857955

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:53

Enthalten in:

Nature genetics - 53(2021), 12 vom: 02. Dez., Seite 1698-1711

Sprache:

Englisch

Beteiligte Personen:

Garcia-Alonso, Luz [VerfasserIn]
Handfield, Louis-François [VerfasserIn]
Roberts, Kenny [VerfasserIn]
Nikolakopoulou, Konstantina [VerfasserIn]
Fernando, Ridma C [VerfasserIn]
Gardner, Lucy [VerfasserIn]
Woodhams, Benjamin [VerfasserIn]
Arutyunyan, Anna [VerfasserIn]
Polanski, Krzysztof [VerfasserIn]
Hoo, Regina [VerfasserIn]
Sancho-Serra, Carmen [VerfasserIn]
Li, Tong [VerfasserIn]
Kwakwa, Kwasi [VerfasserIn]
Tuck, Elizabeth [VerfasserIn]
Lorenzi, Valentina [VerfasserIn]
Massalha, Hassan [VerfasserIn]
Prete, Martin [VerfasserIn]
Kleshchevnikov, Vitalii [VerfasserIn]
Tarkowska, Aleksandra [VerfasserIn]
Porter, Tarryn [VerfasserIn]
Mazzeo, Cecilia Icoresi [VerfasserIn]
van Dongen, Stijn [VerfasserIn]
Dabrowska, Monika [VerfasserIn]
Vaskivskyi, Vasyl [VerfasserIn]
Mahbubani, Krishnaa T [VerfasserIn]
Park, Jong-Eun [VerfasserIn]
Jimenez-Linan, Mercedes [VerfasserIn]
Campos, Lia [VerfasserIn]
Kiselev, Vladimir Yu [VerfasserIn]
Lindskog, Cecilia [VerfasserIn]
Ayuk, Paul [VerfasserIn]
Prigmore, Elena [VerfasserIn]
Stratton, Michael R [VerfasserIn]
Saeb-Parsy, Kourosh [VerfasserIn]
Moffett, Ashley [VerfasserIn]
Moore, Luiza [VerfasserIn]
Bayraktar, Omer A [VerfasserIn]
Teichmann, Sarah A [VerfasserIn]
Turco, Margherita Y [VerfasserIn]
Vento-Tormo, Roser [VerfasserIn]

Links:

Volltext

Themen:

Gonadal Steroid Hormones
Journal Article
Receptors, Notch
Research Support, Non-U.S. Gov't
Wnt Proteins

Anmerkungen:

Date Completed 28.12.2021

Date Revised 23.12.2022

published: Print-Electronic

CommentIn: Nat Genet. 2021 Dec;53(12):1628-1630. - PMID 34857955

Citation Status MEDLINE

doi:

10.1038/s41588-021-00972-2

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM333947681