Lin Yu, Qi Yiwen, Yao Yutong, Tong Huan, Chen Lan, Song Weizhou, Li Guojing, Xu Hong, He Xiaoying
International Peace Maternity & Child Health Hospital, Shanghai Key Laboratory of Embryo Original Diseases, Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, The People's Republic of China.
Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Maternal and Fetal Medicine, School of Medicine, Tong Ji University, Shanghai, The People's Republic of China.
FASEB J. 2025 May 15;39(9):e70512. doi: 10.1096/fj.202500116R.
Endometrial polyps are the predominant structural anomalies of the endometrial mucosa observed in unexplained infertility cases, potentially compromising endometrial receptivity and suggesting shared etiological characteristics. However, their comprehensive cell atlas and immune landscape remain inadequately defined. In this study, we employed single-cell RNA sequencing and bulk RNA-seq to systematically analyze ectopic endometrial polyps (EPs) alongside adjacent eutopic endometrial tissues (EUs). This enabled us to delineate alterations in cell composition and transcriptional dynamics across diverse cell types associated with endometrial polyps. Notably, we observed an increase and activation of mast cells, with significant transcriptional profile variations. Through transcription regulatory network analysis, WT1 was identified as a pivotal transcriptional regulator mediating mast cell proliferation in EPs, concomitant with the dysregulation of WT1 target genes involved in cell growth. These findings provide novel insights into the cellular heterogeneity and molecular mechanisms of endometrial polyps at single-cell resolution, presenting potential therapeutic targets for clinical intervention.
子宫内膜息肉是在不明原因不孕症病例中观察到的子宫内膜黏膜的主要结构异常，可能会损害子宫内膜容受性，并提示存在共同的病因特征。然而，它们的综合细胞图谱和免疫景观仍未得到充分界定。在本研究中，我们采用单细胞RNA测序和批量RNA测序，对异位子宫内膜息肉（EPs）以及相邻的在位子宫内膜组织（EUs）进行系统分析。这使我们能够描绘与子宫内膜息肉相关的不同细胞类型中细胞组成和转录动态的变化。值得注意的是，我们观察到肥大细胞增加并被激活，且转录谱有显著变化。通过转录调控网络分析，WT1被确定为介导EPs中肥大细胞增殖的关键转录调节因子，同时涉及细胞生长的WT1靶基因也发生失调。这些发现以单细胞分辨率为子宫内膜息肉的细胞异质性和分子机制提供了新的见解，为临床干预提供了潜在的治疗靶点。
