Single-cell transcriptome profiling of the human endometrium of patients with recurrent implantation failure.
Single-cell transcriptome profiling of the human endometrium of patients with recurrent implantation failure.
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复发性着床失败患者子宫内膜的单细胞转录组分析
作者：
Lai ZZ;Wang Y;Zhou WJ;Liang Z;Shi JW;Yang HL;Xie F;Chen WD;Zhu R;Zhang C;Mei J;Zhao JY;Ye JF;Zhang T;Li MQ
导言：尽管辅助生殖技术（ART）取得了很大的进步，但复发性着床失败（RIF）仍不能有效避免。值得注意的是，调节子宫内膜容受性和分化的细胞特征和通讯，以及其在植入窗口（WOI）的RIF紊乱仍处于初级阶段。目的：在这项研究中，我们使用单细胞RNA测序（scRNA-seq）分析了RIF患者和健康对照者在WOI时间存在的子宫内膜细胞，并提供了WOI时健康和RIF子宫内膜的详细分子和细胞图谱。方法：本研究采用单细胞分辨率对RIF患者（n = 6，年龄范围32 - 35岁）和对照组（n = 3，年龄范围29 - 35岁）的子宫内膜进行研究。对RIF和Ctrl患者的子宫内膜进行单细胞rna测序和分析。采用免疫荧光、流式细胞术和定量实时聚合酶链反应（qRT-PCR）验证细胞身份和功能。结果：我们在单细胞分辨率下分析了从对照和RIF患者分离的60222个原代人子宫内膜细胞的转录组。我们发现，与对照子宫内膜相比，RIF患者的四种主要子宫内膜成纤维细胞样细胞中子宫内膜容受性相关基因的表达存在显著差异。我们观察到CD49a+CXCR4+NK细胞与RIF成比例减少。高水平孕酮受体、自噬和外泌体的CD63highPGRhigh子宫内膜上皮细胞亚群的减少可能导致NK细胞亚群的减少。此外，我们还描述了RIF患者的异常分子和细胞特征以及子宫内膜细胞-细胞通讯障碍。结论：我们的研究对RIF的子宫内膜微环境障碍提供了更深入的认识，可能适用于改善不明原因RIF的病因学诊断和治疗。
Introduction: Despite great advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) cannot be effectively avoided. Notably, cellular characteristics and communication that regulate endometrial receptivity and differentiation, and its disorders in RIF at window of implantation (WOI) remain rudimentary. Objectives: In this study, we profiled the endometrial cells present at the WOI timing in RIF patients and healthy controls using single-cell RNA sequencing (scRNA-seq) and provided a detailed molecular and cellular map of a healthy and RIF endometrium at the WOI. Method: In the current study, the endometrium from RIF patient (n = 6; age range, 32 - 35 years) and control (Ctrl) (n = 3; age range, 29 - 35 years) groups were studied at a single-cell resolution. single-cell RNA-seq and analysis were performed on the endometrium of patients with RIF and Ctrl. Immunofluorescence, flow cytometry assays, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to verify cellular identity and function. Results: We profiled the transcriptomes of 60222 primary human endometrial cells isolated from control and RIF patients at a single-cell resolution. We discovered dramatic differential expression of endometrial receptivity-related genes in four major endometrial fibroblast-like cells from RIF patients compared to the control endometrium. We observed that CD49a+CXCR4+NK cells were diminished in proportion with RIF. The decrease in subset of CD63highPGRhigh endometrial epithelial cells with high levels of progesterone receptor, autophagy and exosomes should contribute to the decrease in subset of NK cells. Additionally, we characterized aberrant molecular and cellular characteristics and endometrial cell-cell communication disorders in RIF patients. Conclusion: Our study provides deeper insights into endometrial microenvironment disorder of RIF that are potentially applicable to improving the etiological diagnosis and therapeutics of unexplained RIF.
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影响因子：
82.9
作者：
Cha J;Sun X;Dey SK
通讯作者：
Dey SK
影响因子：
5.8
作者：
Kitaya, K;Yamaguchi, T;Honjo, H
通讯作者：
Honjo, H
DOI：
10.1093/humrep/dew008
发表时间：
2016-04
期刊：
Human reproduction (Oxford, England)
影响因子：
--
作者：
Krjutškov K;Katayama S;Saare M;Vera-Rodriguez M;Lubenets D;Samuel K;Laisk-Podar T;Teder H;Einarsdottir E;Salumets A;Kere J
通讯作者：
Kere J
影响因子：
6.7
作者：
Garrido-Gomez, Tamara;Ruiz-Alonso, Maria;Simon, Carlos
通讯作者：
Simon, Carlos
影响因子：
3.6
作者：
HildPetito, S;Fazleabas, AT;Carson, DD
通讯作者：
Carson, DD