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

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 beha...

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Published inStem cells (Dayton, Ohio) Vol. 28; no. 11; pp. 1981 - 1991
Main Authors Hu, Qirui, Friedrich, Amy M., Johnson, Lincoln V., Clegg, Dennis O.
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2010
Subjects
Cell Differentiation - genetics
Cell Differentiation - physiology
Cell Line
Cell Proliferation
Epigenetic memory
Epithelial Cells - cytology
Epithelial Cells - metabolism
Flow Cytometry
Humans
Immunohistochemistry
Induced pluripotent stem cells
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
Karyotyping
Retinal Pigment Epithelium - cytology
Retinal pigmented epithelium
Reverse Transcriptase Polymerase Chain Reaction
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Summary: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
Bibliography:First published online in STEM CELLS
September 29, 2010.
Disclosure of potential conflicts of interest is found at the end of this article.
Author contributions: Q.H.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; A.M.F.: collection of data; L.V.J.: conception and design, financial support, manuscript writing, final approval of manuscript; D.O.C.: conception and design, financial support, manuscript writing, final approval of manuscript.
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ISSN:1066-5099
1549-4918
DOI:10.1002/stem.531