Memory in Induced Pluripotent Stem Cells: Reprogrammed Human Retinal-Pigmented Epithelial Cells Show Tendency for Spontaneous Redifferentiation
Memory in Induced Pluripotent Stem Cells: Reprogrammed Human Retinal-Pigmented Epithelial Cells Show Tendency for Spontaneous Redifferentiation
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DOI：
10.1002/stem.531
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发表时间：
2010-11-01
期刊：
影响因子：
5.2
通讯作者：
Clegg, Dennis O.
中科院分区：
文献类型：
--
作者：
Hu, Qirui;Friedrich, Amy M.;Clegg, Dennis O.
诱导多能干细胞（iPS）已经通过引入介导多能性的转录因子从多种体细胞类型产生。然而，尚不清楚所有细胞类型都可以被重编程，以及亲本细胞的来源是否最终决定了所得iPS细胞系的行为。我们试图确定人类视网膜色素上皮（RPE）细胞是否可以被重编程，并测试重编程细胞保留其起源的分化倾向方面的“记忆”的假设。我们通过OCT 4、SOX 2、LIN 28和Nanog的慢病毒表达对原代胎儿RPE细胞进行重编程。来自RPE的iPS细胞系表现出与人胚胎干细胞和其他iPS细胞系相似的形态学，表达干细胞标志物，并形成所有三个胚层的含有畸胎瘤的衍生物。为了测试这些iPS细胞是否保留了来自亲本RPE细胞的表观遗传印记，我们分析了它们在去除FGF 2后自发分化回RPE的倾向。我们发现，一些，但不是全部，iPS线表现出显着的偏好再分化成RPE。我们的研究结果表明，RPE细胞可以被重编程为多能性，并表明它们通常保留了以前分化状态的记忆。干细胞2010;28：1981-1991
Induced pluripotent stem (iPS) cells have been generated from a variety of somatic cell types via introduction of transcription factors that mediate pluripotency. However, it is unknown that all cell types can be reprogrammed and whether the origin of the parental cell ultimately determines the behavior of the resultant iPS cell line. We sought to determine whether human retinal-pigmented epithelial (RPE) cells could be reprogrammed, and to test the hypothesis that reprogrammed cells retain a "memory" of their origin in terms of propensity for differentiation. We reprogrammed primary fetal RPE cells via lentiviral expression of OCT4, SOX2, LIN28, and Nanog. The iPS cell lines derived from RPE exhibited morphologies similar to human embryonic stem cells and other iPS cell lines, expressed stem cell markers, and formed teratomas-containing derivatives of all three germ layers. To test whether these iPS cells retained epigenetic imprints from the parental RPE cells, we analyzed their propensity for spontaneous differentiation back into RPE after removal of FGF2. We found that some, but not all, iPS lines exhibited a marked preference for redifferentiation into RPE. Our results show that RPE cells can be reprogrammed to pluripotency, and suggest that they often retain a memory of their previous state of differentiation. STEM CELLS 2010;28:1981-1991