Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium

被引：254

作者：

Brighton, Paul J. ^{[1
]}

Maruyama, Yojiro ^{[1
,2
]}

Fishwick, Katherine ^{[1
]}

Vrljicak, Pavle ^{[1
,3
]}

Tewary, Shreeya ^{[1
,3
]}

Fujihara, Risa ^{[1
,2
]}

Muter, Joanne ^{[1
]}

Lucas, Emma S. ^{[1
,3
]}

Yamada, Taihei ^{[2
]}

Woods, Laura ^{[4
,5
]}

Lucciola, Raffaella ^{[1
]}

Lee, Yie Hou ^{[6
,7
]}

Takeda, Satoru ^{[2
]}

Ott, Sascha ^{[3
]}

Hemberger, Myriam ^{[4
,5
]}

Quenby, Siobhan ^{[1
]}

Brosens, Jan Joris ^{[1
]}

机构：

[1] Univ Warwick, Div Biomed Sci, Clin Sci Res Labs, Warwick Med Sch, Coventry, W Midlands, England

[2] Juntendo Univ, Dept Obstet & Gynecol, Fac Med, Tokyo, Japan

[3] Univ Hosp Coventry & Warwickshire, Tommys Natl Ctr Miscarriage Res, Coventry, W Midlands, England

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

[5] Babraham Inst, Epigenet Programme, Cambridge, England

[6] Duke NUS Med Sch, Obstet & Gynaecol Acad Clin Program, Singapore, Singapore

[7] KK Womens & Childrens Hosp, KK Res Ctr, Singapore, Singapore

来源：

ELIFE | 2017年 / 6卷

基金：

英国生物技术与生命科学研究理事会;

关键词：

CELLULAR SENESCENCE; STROMAL CELLS; EMBRYO IMPLANTATION; DIFFERENTIATION; QUANTIFICATION; PLASTICITY; INTERFACE; FAILURE; BINDING; PROTEIN;

D O I：

10.7554/eLife.31274

中图分类号：

Q [生物科学];

学科分类号：

090105 [作物生产系统与生态工程];

摘要：

In cycling human endometrium, menstruation is followed by rapid estrogen-dependent growth. Upon ovulation, progesterone and rising cellular cAMP levels activate the transcription factor Forkhead box O1 (FOXO1) in endometrial stromal cells (EnSCs), leading to cell cycle exit and differentiation into decidual cells that control embryo implantation. Here we show that FOXO1 also causes acute senescence of a subpopulation of decidualizing EnSCs in an IL-8 dependent manner. Selective depletion or enrichment of this subpopulation revealed that decidual senescence drives the transient inflammatory response associated with endometrial receptivity. Further, senescent cells prevent differentiation of endometrial mesenchymal stem cells in decidualizing cultures. As the cycle progresses, IL-15 activated uterine natural killer (uNK) cells selectively target and clear senescent decidual cells through granule exocytosis. Our findings reveal that acute decidual senescence governs endometrial rejuvenation and remodeling at embryo implantation, and suggest a critical role for uNK cells in maintaining homeostasis in cycling endometrium.

引用

页数：23

共 52 条

[21]

Implications of telomeres and telomerase in endometrial pathology [J].