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富含亮氨酸重复序列的 G 蛋白偶联受体 5(Lgr5)作为一种潜在的人子宫内膜干细胞标志物。

Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) as a putative human endometrial stem cell marker.

机构信息

Fundación IVI-Instituto Universitario IVI-Universidad de Valencia, INCLIVA, Valencia, Spain.

出版信息

Mol Hum Reprod. 2013 Jul;19(7):407-14. doi: 10.1093/molehr/gat014. Epub 2013 Mar 7.

Abstract

The endometrium is recognized for its remarkable regenerative and remodeling capacity. Every month this hormonally regulated organ undergoes cycles of growth (from 0.5-2 to 7 mm), regression and shedding of two-third of the tissue, leading to its monthly renewal that occurs ∼400 times in a woman's reproductive lifetime. Several groups have suggested the existence of a human endometrial somatic stem cell (SSC) population located around the spiral arterioles of the basalis. Different groups have isolated, identified and characterized putative endometrial SSC populations in human endometrium based on the general features of undifferentiated cells, such as slow cycling detected using the 5-bromo-2-deoxyuridine technique or identification of a side population using the Hoechst efflux dye technique. Nevertheless, specific markers to isolate these endometrial SSC have not yet been consistently elucidated. Accumulated evidence based on lineage tracing studies indicates that a surface protein named Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a marker that can identify SSC in several tissues such as small intestine mucosa (endodermal origin), hair follicles (ectodermal origin) or mature kidney nephrons (mesodermal origin). This protein plays a crucial role in the Wnt/β-catenin signaling system by acting on the self-renewal and maintenance of the SSC population. In this work, we present novel data suggestive of Lgr5 as a putative human endometrial SSC marker, and since this is a mesoderm-derived tissue, these findings reinforce the concept that Lgr5 can be considered a universal SSC marker.

摘要

子宫内膜以其显著的再生和重塑能力而闻名。这个受激素调节的器官每个月都会经历生长(从 0.5-2 到 7 毫米)、退化和三分之二组织脱落的周期,导致其每月更新,在女性的生殖寿命中大约发生 400 次。有几个小组提出了位于基底螺旋动脉周围的人类子宫内膜体干细胞(SSC)群体的存在。不同的小组已经根据未分化细胞的一般特征,如使用 5-溴-2-脱氧尿苷技术检测到的缓慢循环或使用 Hoechst 外排染料技术鉴定侧群,从人子宫内膜中分离、鉴定和表征了假定的子宫内膜 SSC 群体。然而,尚未一致阐明用于分离这些子宫内膜 SSC 的特定标志物。基于谱系追踪研究的累积证据表明,一种名为富含亮氨酸重复的 G 蛋白偶联受体 5(Lgr5)的表面蛋白是一种可以识别几种组织中的 SSC 的标志物,如小肠黏膜(内胚层起源)、毛囊(外胚层起源)或成熟肾脏肾单位(中胚层起源)。该蛋白通过作用于 SSC 群体的自我更新和维持,在 Wnt/β-catenin 信号系统中发挥着关键作用。在这项工作中,我们提出了新的有说服力的数据,表明 Lgr5 是一种潜在的人类子宫内膜 SSC 标志物,由于这是一种中胚层来源的组织,这些发现强化了这样一个概念,即 Lgr5 可以被视为普遍的 SSC 标志物。

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