The human endometrium undergoes repetitive regeneration cycles in order to recover the functional layer, shed during menses. The basal layer, which remains in charge of endometrial regeneration in every cycle, contains adult stem or progenitor cells of epithelial and mesenchymal lineage. Some pathologies such as adenomyosis, in which endometrial tissue develops within the myometrium, originate from this layer. It is well known that the balance between adenosine triphosphate (ATP) and adenosine plays a crucial role in stem/progenitor cell physiology, influencing proliferation, differentiation, and migration. The extracellular levels of nucleotides and nucleosides are regulated by the ectonucleotidases, such as the nucleoside triphosphate diphosphohydrolase 2 (NTPDase2). NTPDase2 is a membrane-expressed enzyme found in cells of mesenchymal origin such as perivascular cells of different tissues and the stem cells of adult neurogenic regions. The aim of this study was to characterize the expression of NTPDase2 in human nonpathological cyclic and postmenopausic endometria and in adenomyosis. We examined proliferative, secretory, and atrophic endometria from women without endometrial pathology and also adenomyotic lesions. Importantly, we identified NTPDase2 as the first marker of basal endometrium since other stromal cell markers such as CD10 label the entire stroma. As expected, NTPDase2 was also found in adenomyotic stroma, thus becoming a convenient tracer of these lesions. We did not record any changes in the expression levels or the localization of NTPDase2 along the cycle, thus suggesting that the enzyme is not influenced by the female sex hormones like other previously studied ectoenzymes. Remarkably, NTPDase2 was expressed by the Sushi Domain containing 2 (SUSD2)⁺ endometrial mesenchymal stem cells (eMSCs) found perivascularly, rendering it useful as a cell marker to improve the isolation of eMSCs needed for regenerative medicine therapies.

中文翻译：

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人子宫内膜中的外核苷三磷酸二磷酸水解酶2（NTPDase2）：基础基质和间充质干细胞的新标记。

人类子宫内膜经过反复的再生循环，以恢复月经期间脱落的功能层。在每个周期中负责子宫内膜再生的基底层包含上皮和间充质谱系的成年干细胞或祖细胞。一些疾病，例如子宫腺肌病，子宫内膜组织在子宫内膜内发育，起源于这一层。众所周知，三磷酸腺苷（ATP）和腺苷之间的平衡在干/祖细胞生理中起着至关重要的作用，影响增殖，分化和迁移。核苷酸和核苷的细胞外水平受胞外核苷酸酶（例如核苷三磷酸二磷酸水解酶2（NTPDase2））调节。NTPDase2是一种膜表达酶，存在于间充质来源的细胞中，例如不同组织的血管周细胞和成年神经源性区域的干细胞。这项研究的目的是表征NTPDase2在人类非病理性循环和绝经后子宫内膜以及子宫腺肌病中的表达。我们检查了没有子宫内膜病理学和子宫腺肌病病变的妇女的子宫内膜增生，分泌和萎缩。重要的是，我们将NTPDase2鉴定为基底子宫内膜的第一个标记，因为其他基质细胞标记（例如CD10）标记了整个基质。不出所料，在腺肌症基质中也发现了NTPDase2，因此成为这些病变的便捷示踪剂。我们没有记录整个循环中NTPDase2的表达水平或定位的任何变化，因此表明该酶不像其他先前研究的外切酶一样受女性性激素的影响。值得注意的是，NTPDase2由包含2（SUSD2）的Sushi Domain表达。在血管周围发现⁺子宫内膜间充质干细胞（eMSCs），使其可用作细胞标记物，以改善再生医学疗法所需的eMSCs分离。