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Shenghai Zhang, Jihong Wu; Somatic Epigenetic Memory in iPSC-drived from Adult RPE. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2224.
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iPS can be derived from somatic cells by activation of transcription factors and hold enormous promise in degenerative retinal disease therapy. However, increasing evidence shown that iPSC deviated from ES cells in the expression of genes, epigenomic patterns, and neural differentiation properties. Here, we investigate whether RPE-derived iPSCs represent somatic gene expression and epigenetic memory, which could affect their utility and clinical safety.
In order to perform the systematic comparison of hES and iPS generated from RPE and fibroblasts, methylating-gene microarray and Affymetrix ST 1.0 microarrays were used to analyze whole-genome profiles changes of DNA methylation at single-base resolution and transcriptional profile.
Reprogramming induces a remarkable reconfiguration of the DNA methylation patterns throughout the somatic cell genome, to ES-like states. It showed that iPSC generated from fibroblast and RPE are remarkably similar to human ES cells. Low-passage iPS cells derived from RPE and fibroblast retain a transcriptional memory of their original cells respectively. The persistent expression of somatic genes can be partially explained by incomplete DNA methylation or reactivation. It is important to point out that most of our findings pertain to low-passage (<P15) human iPS cells. Many of the differences relative to ES cells are expected to be attenuated, although possibly not completely abolished.
An evaluation of the DNA methylation status of somatic cell genes may be warranted in the validation of new human iPS cell lines.
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