Wnt信号通路
生物
化生
间质细胞
细胞生物学
基质
上皮
干细胞
舱室(船)
谱系标记
转分化
上皮-间质转换
谱系(遗传)
过渡(遗传学)
斑马鱼
癌症研究
病理
免疫学
祖细胞
遗传学
信号转导
基因
免疫组织化学
医学
海洋学
地质学
作者
Cindrilla Chumduri,Rajendra Kumar Gurumurthy,Hilmar Berger,Oliver Dietrich,Naveen Kumar,Stefanie Koster,Volker Brinkmann,Kirstin Hoffmann,Marina Drabkina,Panagiota Arampatzi,Dajung Son,Uwe Klemm,Hans-Joachim Mollenkopf,Hermann Herbst,Mandy Mangler,Jörg Vogel,Antoine-Emmanuel Saliba,Thomas J. Meyer
标识
DOI:10.1038/s41556-020-00619-0
摘要
The transition zones of the squamous and columnar epithelia constitute hotspots for the emergence of cancer, often preceded by metaplasia, in which one epithelial type is replaced by another. It remains unclear how the epithelial spatial organization is maintained and how the transition zone niche is remodelled during metaplasia. Here we used single-cell RNA sequencing to characterize epithelial subpopulations and the underlying stromal compartment of endo- and ectocervix, encompassing the transition zone. Mouse lineage tracing, organoid culture and single-molecule RNA in situ hybridizations revealed that the two epithelia derive from separate cervix-resident lineage-specific stem cell populations regulated by opposing Wnt signals from the stroma. Using a mouse model of cervical metaplasia, we further show that the endocervical stroma undergoes remodelling and increases expression of the Wnt inhibitor Dickkopf-2 (DKK2), promoting the outgrowth of ectocervical stem cells. Our data indicate that homeostasis at the transition zone results from divergent stromal signals, driving the differential proliferation of resident epithelial lineages.
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