原发性硬化性胆管炎疾病源性iPSCs细胞模型的建立  

Establishment of iPSCs cell model of primary sclerosing cholangitis

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作  者:孙艳[1,2] 石光[1] 胡春梅[1] 张雪[1] 顾佳颖[1] 迟宝荣 SUN Yan;SHI Guang;HU Chunmei;ZHANG Xue;GU Jiaying;CHI Baorong(Department of Oncology and Hematology, the Second Hospital of Jilin University, Jilin 130041;Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, China)

机构地区:[1]吉林大学第二医院肿瘤.血液内科,吉林长春130041 [2]郑州大学第一附属医院消化内科

出  处:《胃肠病学和肝病学杂志》2019年第5期552-555,共4页Chinese Journal of Gastroenterology and Hepatology

基  金:吉林省国际科技合作基金资助项目(20160414037GH)

摘  要:目的探讨原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)疾病源性诱导性多能干细胞(induced pluripotent stem cells,iPSCs)细胞模型的建立。方法采用Oct3/4、Sox2、c-Myc和Klf4 4种转录因子,以仙台病毒为载体重编程PSC患者皮肤成纤维细胞,获得疾病特异性的iPSCs细胞,并对其生物学特性进行鉴定。结果 PSC疾病源性的iPSCs细胞呈典型胚胎干细胞样克隆,流式细胞分析显示高表达Oct4、TRA-1-81、SSEA和Nanog等胚胎干细胞标志性抗原,体外向内、中、外三个胚层诱导分化后均检测到各胚层标志抗原的表达,传代过程中保持稳定正常的染色体核型。结论应用Yamanaka因子和仙台病毒载体成功建立PSC疾病源性iPSCs细胞模型,后续进一步向胆管细胞诱导分化可用于研究疾病的发病机制。Objective To explore the establishment of iPSCs cell model of primary sclerosing cholangitis (PSC). Methods Four transcription factors, Oct3/4, Sox2, c-Myc and Klf4, were used to reprogram skin fibroblasts of PSC patients with sendai virus as the vector to obtain disease-specific iPSCs cells and identify their biological characteristics. Results PSC disease-derived iPSCs were typical embryonic stem cell-like clones, and flow cytometry showed high expressions of Oct4, TRA-1-81, SSEA, Nanog. The expression of each germ layer marker was detected after induced differentiation into three endoderms in vitro. The chromosome karyotype remained stable and normal during passage. Conclusion The PSC disease-derived iPSCs cell model was successfully established by Yamanaka factor and sendai virus vector, and further induced differentiation into bile duct cells could be used to study the pathogenesis of the disease.

关 键 词:原发性硬化性胆管炎 重编程 诱导性多能干细胞 

分 类 号:R575[医药卫生—消化系统]

 

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