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人类子宫内膜的组织学 3D 重建与体内谱系追踪。

Histological 3D reconstruction and in vivo lineage tracing of the human endometrium.

机构信息

Liverpool Women's Hospital NHS Foundation Trust, member of the Liverpool Health partnership, Liverpool, UK.

Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, member of the Liverpool Health partnership, Liverpool, UK.

出版信息

J Pathol. 2020 Aug;251(4):440-451. doi: 10.1002/path.5478. Epub 2020 Jun 30.

DOI:10.1002/path.5478
PMID:32476144
Abstract

Regular menstrual shedding and repair of the endometrial functionalis is unique to humans and higher-order primates. The current consensus postulates endometrial glands to have a single-tubular architecture, where multi-potential stem cells reside in the blind-ending glandular-bases. Utilising fixed samples from patients, we have studied the three-dimensional (3D) micro-architecture of the human endometrium. We demonstrate that some non-branching, single, vertical functionalis glands originate from a complex horizontally interconnecting network of basalis glands. The existence of a multipotent endometrial epithelial stem cell capable of regenerating the entire complement of glandular lineages was demonstrated by in vivo lineage tracing, using naturally occurring somatic mitochondrial DNA mutations as clonal markers. Vertical tracking of mutated clones showed that at least one stem-cell population resides in the basalis glands. These novel findings provide insight into the efficient and scar-less regenerative potential of the human endometrium. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

摘要

周期性的月经脱落和子宫内膜功能层的修复是人类和高级灵长类动物所特有的。目前的共识假设子宫内膜腺体具有单一管状结构,多潜能干细胞存在于盲端的腺体基部。我们利用患者的固定样本,研究了人类子宫内膜的三维(3D)微观结构。我们证明,一些非分支的、单一的、垂直的功能性腺体起源于基底膜腺体复杂的水平相互连接的网络。通过体内谱系追踪,利用天然存在的体线粒体 DNA 突变作为克隆标记,证明了具有再生整个腺体谱系能力的多能子宫内膜上皮干细胞的存在。对突变克隆的垂直追踪表明,至少有一种干细胞群体存在于基底膜腺体中。这些新发现为理解人类子宫内膜的高效和无疤痕再生潜力提供了线索。

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