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

Study of the unique cellular molecular characteristics of moderately intrauterine adhesion based on single-cell RNA sequencing

目的构建人类宫腔粘连(IUA)组织的细胞景观及其分子生物学特征,以便更好地了解其免疫微环境,为临床治疗提供新的思路。方法选取2022年2月至2022年4月在东莞市妇幼保健院接受宫腔镜治疗的4例IUA患者为研究对象。利用宫腔镜采集IUA组织,并根据患者的病史、月经史及IUA状态等评分和分级,样本采集后立即送检。严格按照单细胞RNA测序流程进行文库构建、测序、数据比对和基因表达矩阵构建,之后进行细胞分群UMAP降维分析和基于细胞类型的差异基因分析。结果收集到4例分级为中度的IUA组织样本,共获得27511个细胞转录组,分配到6个细胞谱系,分别为T细胞、单核吞噬细胞、上皮细胞、成纤维细胞、内皮细胞和红细胞。与文献报道的正常子宫组织细胞相比,本研究的4例样本具有不同的细胞分布,IUA0202204号样本中单核吞噬细胞与T细胞的占比明显偏高,提示存在较强的细胞免疫反应。结论描述了中度IUA组织的细胞多样性和异质性,以及各细胞亚群的分子学特征,为进一步研究IUA的发病机制与患者的异质性提供了线索。

Objective To depict the cell landscape and molecular biological characteristics of human intrauterine adhesion(IUA)so as to better understand its immune microenvironment and provide new inspirations for clinical treatment.Methods Four patients with IUA who underwent hysteroscopic treatment at Dongguan Maternal and Child Health Care Hospital from February 2022 to April 2022 were selected as the study subjects.Hysteroscopy was used to collect the tissues of IUA,which were graded based on the patient’s medical history,menstrual history and status of IUA.Library construction,sequencing,single cell data comparison and gene expression matrix construction were carried out in strict accordance with the single cell RNA sequencing process.Thereafter,the UMAP dimension reduction analysis of cell population and genetic analysis were carried out based on the cell types.Results A total of 27511 cell transcripts were obtained from four moderately graded IUA tissue samples and assigned to six cell lineages including T cells,mononuclear phagocytes,epithelial cells,fibroblasts,endothelial cells and erythrocytes.Compared with normal uterine tissue cells,the four samples showed different cell distribution,and the proportions of mononuclear phagocytes and T cells in sample IUA0202204 were significantly increased,suggesting a strong cellular immune response.Conclusion The cell diversity and heterogeneity of moderate IUA tissues have been described.Each cell subgroup has unique molecular characteristics,which may provide new clues for further study of the pathogenesis of IUA and heterogeneity among the patients.