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首页> 外文期刊>Neoplasia: an international journal for oncology research >Nephron Progenitor But Not Stromal Progenitor Cells Give Rise to Wilms Tumors in Mouse Models with β-Catenin Activation or Wt1 Ablation and Igf2 Upregulation
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Nephron Progenitor But Not Stromal Progenitor Cells Give Rise to Wilms Tumors in Mouse Models with β-Catenin Activation or Wt1 Ablation and Igf2 Upregulation

机译：Nephron祖母，但不是基质祖细胞，在小鼠模型中具有β-连环蛋白激活或WT1消融和IGF2上调的威尔姆斯肿瘤

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Wilms tumor, a common childhood tumor of the kidney, is thought to arise from undifferentiated renal mesenchyme. Variable tumor histology and the identification of tumor subsets displaying different gene expression profiles suggest that tumors may arise at different stages of mesenchyme differentiation and that this ontogenic variability impacts tumor pathology, biology, and clinical outcome. To test the tumorigenic potential of different cell types in the developing kidney, we used kidney progenitor-specific Cre recombinase alleles to introduce Wt1 and Ctnnb1 mutations, two alterations observed in Wilms tumor, into embryonic mouse kidney, with and without biallelic Igf2 expression, another alteration that is observed in a majority of tumors. Use of a Cre allele that targets nephron progenitors to introduce a Ctnnb1 mutation that stabilizes β-catenin resulted in the development of tumors with a predominant epithelial histology and a gene expression profile in which genes characteristic of early renal mesenchyme were not expressed. Nephron progenitors with Wt1 ablation and Igf2 biallelic expression were also tumorigenic but displayed a more triphasic histology and expressed early metanephric mesenchyme genes. In contrast, the targeting of these genetic alterations to stromal progenitors did not result in tumors. These data demonstrate that committed nephron progenitors can give rise to Wilms tumors and that committed stromal progenitors are less tumorigenic, suggesting that human Wilms tumors that display a predominantly stromal histology arise from mesenchyme before commitment to a stromal lineage.
机译：Wilms肿瘤，肾脏的常见儿童肿瘤，被认为是从未分化的肾间表单产生的。可变肿瘤组织学和显示不同基因表达谱的肿瘤子集的鉴定表明，在间充质分化的不同阶段可能出现肿瘤，这种血细胞变异性会影响肿瘤病理，生物学和临床结果。为了测试在发育肾脏中不同细胞类型的致瘤潜力，我们使用肾祖细胞特异性Cre重组酶等位基因来引入WT1和CTNNB1突变，在威尔姆斯肿瘤中观察到两种改变，进入胚胎小鼠肾脏，有和没有双挠曲IGF2表达，另一种在大多数肿瘤中观察到的改变。使用靶向肾祖祖的CRNNB1突变的CRNNB1突变，稳定β-catenin导致具有主要上皮组织学的肿瘤的发育，以及未表达早期肾间表表现的基因特征的基因表达谱。 WT1消融和IGF2双曲线表达的肾龙祖细胞也致致致瘤，但展示了更自动的组织学并表达了早期的Metanephric间充质基因。相反，这些遗传改变对基质祖细胞的靶向不会导致肿瘤。这些数据表明，犯罪的肾血管祖细胞可能会产生威尔姆斯肿瘤，并且犯下的基质祖细胞较少的致瘤症，表明在对基质谱系的承诺之前，从间充质组织出现主要组织学的人威尔姆人肿瘤。

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