Memory in Induced Pluripotent Stem Cells: Reprogrammed Human Retinal-Pigmented Epithelial Cells Show Tendency for Spontaneous Redifferentiation

被引:132
|
作者
Hu, Qirui [1 ,2 ]
Friedrich, Amy M. [1 ,2 ]
Johnson, Lincoln V. [1 ,2 ,3 ]
Clegg, Dennis O. [1 ,2 ,3 ,4 ]
机构
[1] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA
[2] Univ Calif Santa Barbara, Ctr Stem Cell Biol & Engn, Santa Barbara, CA 93106 USA
[3] Univ Calif Santa Barbara, Ctr Study Macular Degenerat, Santa Barbara, CA 93106 USA
[4] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA
关键词
Induced pluripotent stem cells; Retinal pigmented epithelium; Epigenetic memory; HUMAN SOMATIC-CELLS; EPIGENETIC MEMORY; IPS CELLS; B-CELLS; GENERATION; DIFFERENTIATION; MOUSE; FIBROBLASTS; EXPRESSION; DERIVATION;
D O I
10.1002/stem.531
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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
引用
收藏
页码:1981 / 1991
页数:11
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