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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 18 NOV 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 11, pages 1981–1991, November 2010
How to Cite
Hu, Q., Friedrich, A. M., Johnson, L. V. and Clegg, D. O. (2010), Memory in Induced Pluripotent Stem Cells: Reprogrammed Human Retinal-Pigmented Epithelial Cells Show Tendency for Spontaneous Redifferentiation. STEM CELLS, 28: 1981–1991. doi: 10.1002/stem.531
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.
First published online in STEM CELLS EXPRESS September 29, 2010.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue published online: 18 NOV 2010
- Article first published online: 18 NOV 2010
- Accepted manuscript online: 29 SEP 2010 10:40AM EST
- Manuscript Accepted: 14 SEP 2010
- Manuscript Received: 27 APR 2010
- California Institute for Regenerative Medicine CIRM. Grant Numbers: T3-00009, CL1-00521-1
- US Army Research Office via the Institute for Creative Biotechnologies at UCSB. Grant Number: UARC 2/W911NF-09-D-0001
- Induced pluripotent stem cells;
- Retinal pigmented epithelium;
- Epigenetic memory
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