Endogenous KLF4 Expression in Human Fetal Endothelial Cells Allows for Reprogramming to Pluripotency With Just OCT3/4 and SOX2-Brief Report
Endogenous KLF4 Expression in Human Fetal Endothelial Cells Allows for Reprogramming to Pluripotency With Just OCT3/4 and SOX2-Brief Report
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DOI：
10.1161/atvbaha.110.206540
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发表时间：
2010-10-01
影响因子：
8.7
通讯作者：
Yen, B. Linju
中科院分区：
文献类型：
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作者：
Ho, Pai-Jiun;Yen, Men-Luh;Yen, B. Linju
目的：引入4个转录因子-c- myc、OCT3/4、SOX2和klf4 -可重编程体细胞恢复多能性。然而，一些使用的因素是致癌的，使得治疗应用不可行。虽然使用表达高内源性这些因子水平的成体干细胞允许用较少的外源性基因进行重编程，但这种细胞很罕见，可能已经积累了基因突变。我们的目标是重新编程没有致癌因素的人类体细胞。我们发现，在人脐静脉内皮细胞（HUVECs）中高内源性表达KLF4可以产生诱导多能干细胞（iPSCs），仅含有2种非致癌因子，OCT3/4和SOX2。方法与结果：用含OCT4和SOX2的慢病毒感染huvecs生成iPSCs。这些2因子HUVEC iPSCs在形态上与胚胎干细胞相似，表达内源性多能性标记，在体外和体内都能向所有3种胚层分化。结论：仅在2种非致癌因子作用下，HUVECs就能生成ipscs。利用胎儿细胞进行无致癌因子的重编程，可能为人类iPSC研究提供一种有效的体外模型，以及一种可能用于治疗的新来源。（中国生物医学工程学报，2010;30:1905-1907）
Objective-The introduction of 4 transcription factors-c-MYC, OCT3/4, SOX2, and KLF4-can reprogram somatic cells back to pluripotency. However, some of the factors used are oncogenic, making therapeutic application unfeasible. Although the use of adult stem cells expressing high endogenous levels of some of these factors allows for reprogramming with fewer exogenous genes, such cells are rare and may have accumulated genetic mutations. Our goal was to reprogram human somatic cells without oncogenic factors. We found that high endogenous expression of KLF4 in human umbilical vein endothelial cells (HUVECs) allows for generation of induced pluripotent stem cells (iPSCs) with just 2 nononcogenic factors, OCT3/4 and SOX2.Methods and Results-HUVECs were infected with lentivirus containing OCT4 and SOX2 for generation of iPSCs. These 2-factor HUVEC iPSCs were morphologically similar to embryonic stem cells, express endogenous pluripotency markers postreprogramming, and can differentiate toward lineages of all 3 germ layers both in vitro and in vivo.Conclusion-iPSCs can be generated from HUVECs with only 2 nononcogenic factors. The use of fetal cells for reprogramming without oncogenic factors may provide an efficient in vitro model for human iPSC research, as well as a novel source for possible therapeutic use. (Arterioscler Thromb Vasc Biol. 2010;30:1905-1907.)