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表达 slug 基因的小鼠前列腺上皮细胞具有更高的干细胞潜能。

Slug-expressing mouse prostate epithelial cells have increased stem cell potential.

机构信息

Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic.

Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic; Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne's University Hospital Brno, Pekařská 53, 656 91 Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.

出版信息

Stem Cell Res. 2020 Jul;46:101844. doi: 10.1016/j.scr.2020.101844. Epub 2020 May 12.

Abstract

Deciphering the properties of adult stem cells is crucial for understanding of their role in healthy tissue and in cancer progression as well. Both stem cells and cancer stem cells have shown association with epithelial-to-mesenchymal transition (EMT) in various tissue types. Aiming to investigate the epithelial and mesenchymal phenotypic traits in adult mouse prostate, we sorted subpopulations of basal prostate stem cells (mPSCs) and assessed the expression levels of EMT regulators and markers with custom-designed gene expression array. The population of mPSCs defined by a Lin/Sca-1CD49f/Trop-2 (LSC Trop-2) surface phenotype was enriched in mesenchymal markers, especially EMT master regulator Slug, encoded by the Snai2 gene. To further dissect the role of Slug in mPSCs, we used transgenic Snai2 reporter mouse strain. Using this model, we confirmed the presence of mesenchymal traits and increase of organoid forming capacity in Slug population of mPSCs. The Slug-derived organoids comprised all prostate epithelial cell types - basal, luminal, and neuroendocrine. Collectively, these data uncover the important role of Slug expression in the physiology of mouse prostate stem cells.

摘要

解析成体干细胞的特性对于理解其在健康组织中的作用以及在癌症进展中的作用至关重要。干细胞和癌症干细胞都与各种组织类型中的上皮-间充质转化(EMT)有关。为了研究成年小鼠前列腺中的上皮和间充质表型特征,我们对基底前列腺干细胞(mPSC)进行了亚群分选,并使用定制的基因表达阵列评估了 EMT 调节因子和标志物的表达水平。由 Lin/Sca-1CD49f/Trop-2(LSC Trop-2)表面表型定义的 mPSC 群体富含间充质标志物,特别是 EMT 主调节因子 Slug,由 Snai2 基因编码。为了进一步剖析 Slug 在 mPSC 中的作用,我们使用了转基因 Snai2 报告小鼠品系。使用该模型,我们证实了 mPSC 中 Slug 群体存在间充质特征和类器官形成能力增加。Slug 衍生的类器官包含所有前列腺上皮细胞类型-基底、腔和神经内分泌。总之,这些数据揭示了 Slug 表达在小鼠前列腺干细胞生理学中的重要作用。

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