PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■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,在整个月经周期中驱动转录程序的免疫微环境的去卷积是理解子宫内膜调控生物学的关键。
■这里，我们全面分析了10个人子宫内膜样本中59,397个细胞的单细胞转录组,揭示了整个月经周期的动态细胞异质性.
■我们确定了两种血管周围细胞亚型，子宫内膜中的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）活性，并将关键TF与不同免疫细胞类型的转录输出相关联，强调子宫内膜转录调控的重要性。子宫内膜中各种类型细胞之间的动态相互作用有助于调节分泌分化的一系列生物学途径。整合在子宫内膜和535子宫内膜癌（EC）的大量转录组中鉴定的分子生物标志物，我们揭示了5种基于RNA的EC分子亚型,具有高度的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，我们的研究结果揭示了子宫内膜的动态免疫微环境,并为基于RNA的子宫内膜异位症和子宫内膜癌治疗的未来发展提供了新的见解.
■这里，我们全面分析了10个人子宫内膜样本中59,397个细胞的单细胞转录组,揭示了整个月经周期的动态细胞异质性.
■我们确定了两种血管周围细胞亚型，子宫内膜中的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）活性，并将关键TF与不同免疫细胞类型的转录输出相关联，强调子宫内膜转录调控的重要性。子宫内膜中各种类型细胞之间的动态相互作用有助于调节分泌分化的一系列生物学途径。整合在子宫内膜和535子宫内膜癌（EC）的大量转录组中鉴定的分子生物标志物，我们揭示了5种基于RNA的EC分子亚型,具有高度的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，我们的研究结果揭示了子宫内膜的动态免疫微环境,并为基于RNA的子宫内膜异位症和子宫内膜癌治疗的未来发展提供了新的见解.
