SSEA-1子宫内膜上皮祖细胞的转录谱分析揭示了它们在子宫内膜再生、重塑和内环境稳定中的作用。
Transcriptional Profiling of SSEA-1 Endometrial Epithelial Progenitor Cells Highlights Their Role in Endometrial Regeneration, Remodeling, and Homeostasis.
作者信息
Al-Lamee Hannan, Soul Jamie, Green Daniel, Drury Josephine, Hill Christopher J, Vasieva Olga, Valentijn Anthony, Maclean Alison, Drakeley Andrew, Tempest Nicola, Hapangama Dharani K
机构信息
Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, Centre for Women's Health Research, University of Liverpool, Member of Liverpool Health Partners, Liverpool, UK.
Hewitt Centre for Reproductive Medicine, Liverpool Women's NHS Foundation Trust, Liverpool, UK.
出版信息
FASEB J. 2025 May 15;39(9):e70578. doi: 10.1096/fj.202402861R.
Stage-specific embryonic antigen-1 (SSEA-1) endometrial epithelial cells (EECs) assume the postulated stem/progenitor cell niche within the human endometrium. Previous studies have demonstrated that isolated SSEA-1 cells have a higher capacity to generate organoids in a three-dimensional matrix, a lower steroid hormone receptor expression, and higher telomerase activity with longer telomere lengths. Here, we present the transcriptomic profile of isolated SSEA-1 EECs from eight endometrial biopsies compared to SSEA-1 EECs. Transcriptome and pathway analysis indicate that SSEA-1 EECs play an important role in endometrial regeneration, remodeling and neovascularization as expected from a basal progenitor population. We show that SSEA-1 EECs play a role in endometrial tissue homeostasis and tumor suppression, and bioinformatically identify potential upstream regulators such as SPDEF and TGFB1, which may be involved in these mechanisms. In vitro EEC organoid models also demonstrate SSEA-1 EECs to exhibit estrogen responsive proliferation evidenced by stronger immunostaining for progesterone receptor and Ki-67. Our data further suggest a more quiescent, less hormone responsive phenotype for SSEA-1 EECs that co-localize to SOX9 EECs within in silico analysis, thus validating previous studies.
阶段特异性胚胎抗原-1(SSEA-1)子宫内膜上皮细胞(EECs)假定存在于人类子宫内膜内的干细胞/祖细胞生态位。先前的研究表明,分离出的SSEA-1细胞在三维基质中生成类器官的能力更高,类固醇激素受体表达较低,端粒酶活性较高且端粒长度更长。在此,我们展示了与SSEA-1 EECs相比,从八份子宫内膜活检样本中分离出的SSEA-1 EECs的转录组概况。转录组和通路分析表明,正如基础祖细胞群体所预期的那样,SSEA-1 EECs在子宫内膜再生、重塑和新血管形成中发挥重要作用。我们表明,SSEA-1 EECs在子宫内膜组织稳态和肿瘤抑制中发挥作用,并通过生物信息学方法鉴定出潜在的上游调节因子,如SPDEF和TGFB1,它们可能参与这些机制。体外EEC类器官模型还表明,SSEA-1 EECs表现出雌激素反应性增殖,这通过对孕激素受体和Ki-67更强的免疫染色得以证明。我们的数据进一步表明,在计算机分析中与SOX9 EECs共定位的SSEA-1 EECs具有更静止、激素反应性更低的表型,从而验证了先前的研究。
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