Xu Gang, Pan Tao, Li Si, Guo Jing, Zhang Ya, Xu Qi, Chen Renwei, Ma Yanlin, Li Yongsheng
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China, Harbin, 150081, People's Republic of China.
Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Reproductive Medical Center, National Center for International Research, The First Affiliated Hospital of Hainan Medical University, College of Biomedical Information and Engineering, Hainan Medical University, Haikou, Hainan, 571199, People's Republic of China.
Immunotargets Ther. 2024 Jul 16;13:349-366. doi: 10.2147/ITT.S470994. eCollection 2024.
The heterogeneity and dynamic changes of endometrial cells have a significant impact on health as they determine the normal function of the endometrium during the menstrual cycle. Dysfunction of the endometrium can lead to the occurrence of various gynecological diseases. Therefore, deconvolution of immune microenvironment that drives transcriptional programs throughout the menstrual cycle is key to understand regulatory biology of endometrium.
Herein, we comprehensively analyzed single-cell transcriptome of 59,397 cells across ten human endometrium samples and revealed the dynamic cellular heterogeneity throughout the menstrual cycle.
We identified two perivascular cell subtypes, four epithelial subtypes and four fibroblast cell types in endometrium. Moreover, we inferred the cell type-specific transcription factor (TF) activities and linked critical TFs to transcriptional output of diverse immune cell types, highlighting the importance of transcriptional regulation in endometrium. Dynamic interactions between various types of cells in endometrium contribute to a range of biological pathways regulating differentiation of secretory. Integration of the molecular biomarkers identified in endometrium and bulk transcriptome of 535 endometrial cancers (EC), we revealed five RNA-based molecular subtypes of EC with highly intratumoral heterogeneity and different clinical manifestations. Mechanism analysis uncovered clinically relevant pathways for pathogenesis of EC.
In summary, our results revealed the dynamic immune microenvironment of endometrium and provided novel insights into future development of RNA-based treatments for endometriosis and endometrial carcinoma.
子宫内膜细胞的异质性和动态变化对健康有重大影响，因为它们决定了月经周期中子宫内膜的正常功能。子宫内膜功能障碍可导致各种妇科疾病的发生。因此，解析在整个月经周期驱动转录程序的免疫微环境，是理解子宫内膜调节生物学的关键。
在此，我们全面分析了来自十个人类子宫内膜样本的59397个细胞的单细胞转录组，并揭示了整个月经周期中动态的细胞异质性。
我们在子宫内膜中鉴定出两种血管周围细胞亚型、四种上皮亚型和四种成纤维细胞类型。此外，我们推断了细胞类型特异性转录因子（TF）的活性，并将关键TF与多种免疫细胞类型的转录输出联系起来，突出了转录调控在子宫内膜中的重要性。子宫内膜中各种类型细胞之间的动态相互作用有助于一系列调节分泌细胞分化的生物学途径。整合在子宫内膜中鉴定出的分子生物标志物和535例子宫内膜癌（EC）的 bulk转录组，我们揭示了EC的五种基于RNA的分子亚型，具有高度的肿瘤内异质性和不同的临床表现。机制分析揭示了EC发病机制的临床相关途径。
总之，我们的结果揭示了子宫内膜的动态免疫微环境，并为未来基于RNA的子宫内膜异位症和子宫内膜癌治疗的发展提供了新的见解。
