Evidence of the monoclonal composition of human endometrial epithelial glands and mosaic pattern of clonal distribution in luminal epithelium
Evidence of the monoclonal composition of human endometrial epithelial glands and mosaic pattern of clonal distribution in luminal epithelium
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DOI：
10.1016/s0002-9440(10)63653-x
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发表时间：
2003-07-01
影响因子：
6
通讯作者：
Inoue, M
中科院分区：
文献类型：
--
作者：
Tanaka, M;Kyo, S;Inoue, M
子宫内膜。是一种高度再生的组织，在植入中起着至关重要的作用。我们检查了克隆。这种独特的组织的腺细胞以及腔上皮的构成。使用胶原酶为基础的消化技术与显微镜操作，我们分离个人子宫内膜腺体，并研究其克隆性使用聚合酶链反应为基础的测定非随机X染色体失活与X连锁雄激素受体基因。分析的大多数腺体由上皮细胞的单克隆群体组成，其中一个腺体表现出雄激素受体基因的异质性丧失。此外，在1 mm（2）区域内的相邻腺体具有克隆性，表明腔上皮的克隆性是区域性的。子宫内膜的克隆性在一项雌性小鼠的研究中得到进一步证实，这些小鼠在母本或父本X染色体上携带绿色荧光蛋白基因。子宫切片的荧光显微镜检查显示，个别子宫内膜腺体完全由荧光或非荧光细胞组成，并且表面上皮细胞在这些细胞类型之间表现出清晰的边界。这些发现表明，单个或多个干细胞具有统一的克隆性存在于每个子宫内膜腺体的底部和发生在这些细胞的遗传变异可能在子宫内膜癌的发生中起着关键作用。子宫内膜表面特异性X染色体失活与胚胎着床的子宫内膜容受性之间的可能联系仍有待澄清。
The endometrium. is a highly regenerative tissue that plays a crucial role in implantation. We examined the clonal. constitution of glandular cells as well as the luminal epithelium of this unique tissue. Using collagenase-based digestion techniques with microscopic manipulation, we isolated individual human endometrial glands and examined their clonality using a polymerase chain reaction-based assay for nonrandom X chromosome inactivation with an X-linked androgen receptor gene. Most of the glands analyzed were composed of monoclonal populations of epithelial cells and one of the glands exhibited a loss of heterogeneity in the androgen receptor gene. In addition, adjacent glands within a 1-mm(2) area shared clonality, suggesting that clonality of the luminal epithelium is regionally defined. The clonality of endometrium was further confirmed in a study of female mice that harbor the green fluorescent protein gene on either the maternal or paternal X chromosome. Fluorescent microscopy of uterine sections revealed that individual endometrial glands consisted completely of either fluorescent or nonfluorescent cells and that the surface epithelium exhibited a clear boundary between these cell types. These findings suggest that single or multiple stem cells with uniform clonality exist on the bottom of each endometrial gland and genetic alterations occurring in such cells may play a critical role in endometrial carcinogenesis. The possible association between area-specific X inactivation of the endometrial surface and the endometrial receptivity of embryo implantation remains to be clarified.