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

被引：354

作者：

Garcia-Alonso, Luz ^{[1
]}

Handfield, Louis-Francois ^{[1
]}

Roberts, Kenny ^{[1
]}

Nikolakopoulou, Konstantina ^{[2
,3
]}

Fernando, Ridma C. ^{[2
,3
]}

Gardner, Lucy ^{[2
,3
]}

Woodhams, Benjamin ^{[1
,4
]}

Arutyunyan, Anna ^{[1
,2
]}

Polanski, Krzysztof ^{[1
]}

Hoo, Regina ^{[1
,2
]}

Sancho-Serra, Carmen ^{[1
]}

Li, Tong ^{[1
]}

Kwakwa, Kwasi ^{[4
]}

Tuck, Elizabeth ^{[1
]}

Lorenzi, Valentina ^{[1
]}

Massalha, Hassan ^{[1
,5
]}

Prete, Martin ^{[1
]}

Kleshchevnikov, Vitalii ^{[1
]}

Tarkowska, Aleksandra ^{[1
]}

Porter, Tarryn ^{[1
]}

Mazzeo, Cecilia Icoresi ^{[1
]}

van Dongen, Stijn ^{[1
]}

Dabrowska, Monika ^{[1
]}

Vaskivskyi, Vasyl ^{[1
]}

Mahbubani, Krishnaa T. ^{[6
,7
]}

Park, Jong-Eun ^{[1
]}

Jimenez-Linan, Mercedes ^{[8
]}

Campos, Lia ^{[1
]}

Kiselev, Vladimir Yu. ^{[1
]}

Lindskog, Cecilia ^{[9
]}

Ayuk, Paul ^{[10
]}

Prigmore, Elena ^{[1
]}

Stratton, Michael R. ^{[1
]}

Saeb-Parsy, Kourosh ^{[7
,11
]}

Moffett, Ashley ^{[2
,3
]}

Moore, Luiza ^{[1
]}

Bayraktar, Omer A. ^{[1
]}

Teichmann, Sarah A. ^{[1
]}

Turco, Margherita Y. ^{[2
,3
,12
]}

Vento-Tormo, Roser ^{[1
,2
]}

机构：

[1] Wellcome Sanger Inst, Cambridge, England

[2] Univ Cambridge, Ctr Trophoblast Res, Cambridge, England

[3] Univ Cambridge, Dept Pathol, Cambridge, England

[4] Wellcome Genome Campus, EMBL EBI, Hinxton, England

[5] Univ Cambridge, Cavendish Lab, Theory Condensed Matter Grp, Cambridge, England

[6] Univ Cambridge, Dept Haematol, Cambridge, England

[7] NIHR Cambridge Biomed Res Ctr, Cambridge Biorepository Translat Med CBTM, Cambridge, England

[8] Cambridge Univ Hosp NHS Fdn Trust, Dept Pathol, Cambridge, England

[9] Uppsala Univ, Genet & Pathol & Sci Life Lab, Dept Immunol, Uppsala, Sweden

[10] Newcastle Upon Tyne Hosp NHS Fdn Trust, Dept Womens Serv, Newcastle Upon Tyne, Tyne & Wear, England

[11] Univ Cambridge, Dept Surg, Cambridge, England

[12] Friedrich Miescher Inst Biomed Res, Basel, Switzerland

来源：

NATURE GENETICS | 2021年 / 53卷 / 12期

基金：

英国惠康基金;

关键词：

STEM/PROGENITOR CELLS; LONG-TERM; MOUSE; ORGANOIDS; HETEROGENEITY; EXPRESSION; PHYSIOLOGY; EVOLUTION; CAPTURE; SEQ;

D O I：

10.1038/s41588-021-00972-2

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1698 / +

页数：37

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