CFTR constrains the differentiation from mouse embryonic stem cells to intestine lineage cells
CFTR constrains the differentiation from mouse embryonic stem cells to intestine lineage cells
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CFTR限制小鼠胚胎干细胞向肠系细胞的分化
DOI：
10.1016/j.bbrc.2019.01.100
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发表时间：
2019-03-05
影响因子：
3.1
通讯作者：
Yuan, Ping
中科院分区：
文献类型：
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作者：
Li, Peng;Singh, Jyotsana;Yuan, Ping
囊性纤维化跨膜传导调节因子（CFTR）是一种跨膜Cl-和HCO3-转运蛋白，其功能障碍可导致囊性纤维化（CF）和多种先天性疾病。CF患者中最常见的突变是DF508，患者发生胃肠道肿瘤的风险增加。为了探讨DF508-CF患者高癌风险的病因，我们从小鼠DF508-CFTR胚胎干细胞（ES）中提取胚胎干细胞，并将其作为一种新的体外模型，从发育角度研究CFTR的作用。我们发现DF508-CFTR ES细胞的自我更新特性是完整的。然而，在DF508-CFTR ES细胞分化的细胞中，肠谱系的分化、肠祖细胞和主要肠分化细胞标志物的表达显著上调。因此，CFTR在肠系分化中起重要作用。此外，畸胎瘤形成的DF508-CFTR ES细胞增殖、迁移和上皮间质转化相关标记基因的表达增强，表明CFTR具有抑瘤作用。综上所述，我们衍生的DF508-CFTR ES细胞可以作为体外研究CF疾病病因和体内恶性畸胎瘤形成的新模型。(C) 2019 Elsevier Inc.版权所有。
Cystic fibrosis transmembrane conductance regulator (CFTR) is a transmembrane Cl- and HCO3- trans- porter and its malfunction leads to cystic fibrosis (CF) and multiple congenital diseases. The most common mutation in CF patient is DF508 and the patients have increased risk in developing gastrointestinal tumors. To explore the etiology of high cancer risk in DF508-CF patients, we have derived mouse DF508-CFTR embryonic stem (ES) cells and use it as a novel in vitro model to study the role of CFTR from developmental angle. We found the self-renewal properties are intact in DF508-CFTR ES cells. Nevertheless, the differentiation of intestine lineage, the expression of intestine progenitor and major intestine differentiated cell markers is significantly upregulated in DF508-CFTR ES cell differentiated cells. Therefore, CFTR plays an important role in intestine lineage differentiation. Besides, DF508-CFTR ES cells formed teratomas demonstrated enhanced expressions of cell proliferation, migration and epithelial mesenchymal transition associated marker genes, indicating the tumor suppressive role of CFTR. Taken together, our derived DF508-CFTR ES cells can serve as a new model to study the etiology of CF disease in vitro and malignant teratoma formation in vivo. (C) 2019 Elsevier Inc. All rights reserved.