人类子宫内膜的单细胞组学研究进展

doi:10.12280/gjszjk.20240094

摘要/Abstract

摘要：

子宫内膜中各种亚型细胞的表达和功能对于维持正常子宫内膜功能、提供胚胎植入环境非常重要。近年单细胞组学研究因其可以在单个细胞水平上对不同来源、不同时期子宫内膜进行高通量测序，逐渐成为子宫内膜相关基础研究和临床应用的一个重要研究手段。通过对子宫内膜相关单细胞组学的研究进行综述，包括子宫内膜生理状态，以及复发性流产、子宫内膜异位症、子宫腺肌病、薄型子宫内膜、宫腔粘连、反复种植失败以及子宫内膜癌等病理情况下子宫内膜单细胞层面差异、细胞间相互作用。更深入地理解单细胞组学在子宫内膜研究中的应用，有助于揭示子宫内膜相关疾病的病理生理机制。

关键词: 子宫内膜, 单细胞分析, 高通量核苷酸序列分析, 容受性, 胚胎植入

Abstract:

The expression and function of various subtypes of cells in the endometrium are crucial for maintaining normal endometrial function and providing an environment for embryo implantation. In recent years, the single-cell omics has gradually become an important tool for the basic research and clinical application related to endometrium, as it can perform the high-throughput sequencing of endometrium from different sources and stages at the single-cell level. This article provides a systematic review of existing studies on the single-cell omics related to the endometrium, including the physiological status of the endometrium, as well as the single-cell differences and intercellular interactions in pathological conditions such as recurrent spontaneous abortion, endometriosis, adenomyosis, thin endometrium, intrauterine adhesions, repeated implantation failures and endometrial cancer. The deeper understanding of the application of single-cell omics of endometrium is helpful for us to reveal the pathophysiological mechanisms of the endometrium-related diseases.

Key words: Endometrium, Single-cell analysis, High-throughput nucleotide sequencing, Receptivity, Embryo implantation

姜乐然, 张园, 王琳, 刁飞扬. 人类子宫内膜的单细胞组学研究进展[J]. 国际生殖健康/计划生育杂志, 2024, 43(3): 216-221.

JIANG Le-ran, ZHANG Yuan, WANG Lin, DIAO Fei-yang. Research Progress in Single-Cell Omics of Human Endometrium[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(3): 216-221.

参考文献 31

[1]	Giudice LC. Multidimensional transcriptomic mapping of human endometrium at single-cell resolution[J]. Nat Med, 2020, 26(10):1513-1514. doi: 10.1038/s41591-020-1075-1.
[2]	Domar AD, Rooney K, Hacker MR, et al. Burden of care is the primary reason why insured women terminate in vitro fertilization treatment[J]. Fertil Steril, 2018, 109(6):1121-1126. doi: 10.1016/j.fertnstert.2018.02.130.
[3]	Bui AH, Timmons DB, Young SL. Evaluation of endometrial receptivity and implantation failure[J]. Curr Opin Obstet Gynecol, 2022, 34(3):107-113. doi: 10.1097/GCO.0000000000000783.
[4]	Ruiz-Alonso M, Valbuena D, Gomez C, et al. Endometrial Receptivity Analysis (ERA): data versus opinions[J]. Hum Reprod Open, 2021, 2021(2): hoab011. doi: 10.1093/hropen/hoab011.
[5]	Li J, Wang L, Ding J, et al. Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration[J]. Front Immunol, 2022, 13:826198. doi: 10.3389/fimmu.2022.826198.
[6]	Wang W, Vilella F, Alama P, et al. Single-cell transcriptomic atlas of the human endometrium during the menstrual cycle[J]. Nat Med, 2020, 26(10):1644-1653. doi: 10.1038/s41591-020-1040-z.
[7]	Fang Z, Tian Y, Sui C, et al. Single-Cell Transcriptomics of Proliferative Phase Endometrium: Systems Analysis of Cell-Cell Communication Network Using CellChat[J]. Front Cell Dev Biol, 2022, 10:919731. doi: 10.3389/fcell.2022.919731.
[8]	Vento-Tormo R, Efremova M, Botting RA, et al. Single-cell reconstruction of the early maternal-fetal interface in humans[J]. Nature, 2018, 563(7731):347-353. doi: 10.1038/s41586-018-0698-6.
[9]	Dunselman GA, Vermeulen N, Becker C, et al. ESHRE guideline: management of women with endometriosis[J]. Hum Reprod, 2014, 29(3):400-412. doi: 10.1093/humrep/det457.
[10]	Windsperger K, Vondra S, Lackner AI, et al. Densities of decidual high endothelial venules correlate with T-cell influx in healthy pregnancies and idiopathic recurrent pregnancy losses[J]. Hum Reprod, 2020, 35(11):2467-2477. doi: 10.1093/humrep/deaa234.
[11]	Du L, Deng W, Zeng S, et al. Single-cell transcriptome analysis reveals defective decidua stromal niche attributes to recurrent spontaneous abortion[J]. Cell Prolif, 2021, 54(11):e13125. doi: 10.1111/cpr.13125.
[12]	Lucas ES, Vrljicak P, Muter J, et al. Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window[J]. Commun Biol, 2020, 3(1):37. doi: 10.1038/s42003-020-0763-1. pmid: 31965050
[13]	Mor G, Aldo P, Alvero AB. The unique immunological and microbial aspects of pregnancy[J]. Nat Rev Immunol, 2017, 17(8):469-482. doi: 10.1038/nri.2017.64. pmid: 28627518
[14]	Chen P, Zhou L, Chen J, et al. The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss[J]. Front Immunol, 2021, 12:689019. doi: 10.3389/fimmu.2021.689019.
[15]	Saunders P, Horne AW. Endometriosis: Etiology, pathobiology, and therapeutic prospects[J]. Cell, 2021, 184(11):2807-2824. doi: 10.1016/j.cell.2021.04.041. pmid: 34048704
[16]	Tan Y, Flynn WF, Sivajothi S, et al. Single-cell analysis of endometriosis reveals a coordinated transcriptional programme driving immunotolerance and angiogenesis across eutopic and ectopic tissues[J]. Nat Cell Biol, 2022, 24(8):1306-1318. doi: 10.1038/s41556-022-00961-5. pmid: 35864314
[17]	Fonseca M, Haro M, Wright KN, et al. Single-cell transcriptomic analysis of endometriosis[J]. Nat Genet, 2023, 55(2):255-267. doi: 10.1038/s41588-022-01254-1. pmid: 36624343
[18]	Wood C. Adenomyosis: difficult to diagnose, and difficult to treat[J]. Diagn Ther Endosc, 2001, 7(2):89-95. doi: 10.1155/DTE.7.89. pmid: 18493552
[19]	Niu W, Zhang Y, Liu H, et al. Single-Cell Profiling Uncovers the Roles of Endometrial Fibrosis and Microenvironmental Changes in Adenomyosis[J]. J Inflamm Res, 2023, 16:1949-1965. doi: 10.2147/JIR.S402734. pmid: 37179754
[20]	Yildiz S, Kinali M, Wei JJ, et al. Adenomyosis: single-cell transcriptomic analysis reveals a paracrine mesenchymal-epithelial interaction involving the WNT/SFRP pathway[J]. Fertil Steril, 2023, 119(5):869-882. doi: 10.1016/j.fertnstert.2023.01.041. pmid: 36736810
[21]	Gharibeh N, Aghebati-Maleki L, Madani J, et al. Cell-based therapy in thin endometrium and Asherman syndrome[J]. Stem Cell Res Ther, 2022, 13(1):33. doi: 10.1186/s13287-021-02698-8. pmid: 35090547
[22]	Zhang X, Li Y, Chen X, et al. Single-cell transcriptome analysis uncovers the molecular and cellular characteristics of thin endometrium[J]. FASEB J, 2022, 36(3):e22193. doi: 10.1096/fj.202101579R.
[23]	Xu L, Fan Y, Wang J, et al. Dysfunctional intercellular communication and metabolic signaling pathways in thin endometrium[J]. Front Physiol, 2022, 13:1050690. doi: 10.3389/fphys.2022.1050690.
[24]	Lee WL, Liu CH, Cheng M, et al. Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision[J]. Int J Mol Sci, 2021, 22(10):5175. doi: 10.3390/ijms22105175.
[25]	刘运华, 吴志军, 徐州栋, 等. 基于单细胞RNA测序的人类宫腔中度粘连组织中独特的细胞分子学特征研究[J]. 中华医学遗传学杂志, 2023, 40(6):674-679. doi: 10.3760/cma.j.cn511374-20220930-00661.
[26]	Koot YE, Teklenburg G, Salker MS, et al. Molecular aspects of implantation failure[J]. Biochim Biophys Acta, 2012, 1822(12):1943-1950. doi: 10.1016/j.bbadis.2012.05.017. pmid: 22683339
[27]	Lai ZZ, Wang Y, Zhou WJ, et al. Single-cell transcriptome profiling of the human endometrium of patients with recurrent implantation failure[J]. Theranostics, 2022, 12(15):6527-6547. doi: 10.7150/thno.74053.
[28]	Zhang H, Zhang C, Zhang S. Single-Cell RNA Transcriptome of the Human Endometrium Reveals Epithelial Characterizations Associated with Recurrent Implantation Failure[J]. Adv Biol(Weinh), 2024, 8(1):e2300110. doi: 10.1002/adbi.202300110.
[29]	Evans T, Sany O, Pearmain P, et al. Differential trends in the rising incidence of endometrial cancer by type: data from a UK population-based registry from 1994 to 2006[J]. Br J Cancer, 2011, 104(9):1505-1510. doi: 10.1038/bjc.2011.68.
[30]	Ren X, Liang J, Zhang Y, et al. Single-cell transcriptomic analysis highlights origin and pathological process of human endometrioid endometrial carcinoma[J]. Nat Commun, 2022, 13(1):6300. doi: 10.1038/s41467-022-33982-7. pmid: 36273006
[31]	Yu Z, Zhang J, Zhang Q, et al. Single-cell sequencing reveals the heterogeneity and intratumoral crosstalk in human endometrial cancer[J]. Cell Prolif, 2022, 55(6):e13249. doi: 10.1111/cpr.13249.