Reprogramming of EBV-immortalized B-lymphocyte cell lines into induced pluripotent stem cells

Reprogramming of EBV-immortalized B-lymphocyte cell lines into induced pluripotent stem cells
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DOI:
10.1182/blood-2011-03-340620
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发表时间:
2011-08-18
期刊:
影响因子:
20.3
通讯作者:
Jang, Yoon-Young
Jang, Yoon-Young
中科院分区:
医学1区
文献类型:
--
作者:
Choi, Su Mi;Liu, Hua;Jang, Yoon-Young

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EBV永生化的B淋巴细胞系已被广泛储存,用于研究各种疾病,包括罕见的遗传疾病。这些细胞系是利用诱导多能干细胞(IPSC)技术进行疾病建模的重要资源。在这里,我们报告了通过非病毒方法从EBV永生化的B细胞系中产生IPSCs,这些B细胞系来自于多个遗传病患者。EBV细胞系的重编程方法与患者成纤维细胞的重编程方法相比,涉及不同的方案。B细胞系来源的IPSCs表达多能性标记,保留了遗传突变和亲代V(D)J重排特征,并分化为所有3种生殖层细胞类型。这些IPSC中没有整合与重编程相关的转基因或EBV相关基因。对广泛储存的患者B细胞系进行重新编程的能力将为建立人类疾病模型和提供新的药物疗法提供前所未有的机会。(血。2011;118(7):1801-1805)
EBV-immortalized B lymphocyte cell lines have been widely banked for studying a variety of diseases, including rare genetic disorders. These cell lines represent an important resource for disease modeling with the induced pluripotent stem cell (iPSC) technology. Here we report the generation of iPSCs from EBV-immortalized B-cell lines derived from multiple inherited disease patients via a nonviral method. The reprogramming method for the EBV cell lines involves a distinct protocol compared with that of patient fibroblasts. The B-cell line-derived iPSCs expressed pluripotency markers, retained the inherited mutation and the parental V(D)J rearrangement profile, and differentiated into all 3 germ layer cell types. There was no integration of the reprogramming-related transgenes or the EBV-associated genes in these iPSCs. The ability to reprogram the widely banked patient B-cell lines will offer an unprecedented opportunity to generate human disease models and provide novel drug therapies. (Blood. 2011; 118(7): 1801-1805)