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Induced pluripotent stem cells: epigenetic memories and practical implications.

TitleInduced pluripotent stem cells: epigenetic memories and practical implications.
Publication TypeJournal Article
Year of Publication2010
AuthorsSullivan G, Bai Y, Fletcher J, Wilmut I
JournalMol Hum Reprod
Date Published2010 Dec
KeywordsAlgorithms, Animals, Embryonic Stem Cells, Epigenesis, Genetic, Gene Expression, Gene Expression Profiling, Humans, Induced Pluripotent Stem Cells, Mice

Induced pluripotent stem cells (iPSCs) may be obtained by direct reprogramming of different somatic cells to a pluripotent state by forced expression of a handful of transcription factors. It was generally assumed that iPSCs are functionally equivalent to their embryonic stem cell (ESC) counterparts. Recently, a number of research groups have demonstrated that this is not the case, showing that iPSCs retain 'epigenetic memory' of the donor tissue from which they were derived and display skewed differentiation potential. This raises the question whether such cells are fit for experimental, diagnostic or therapeutic purpose. A brief survey of the literature illustrates that differences at both epigenetic and transcriptome level are observed between various pluripotent stem cell populations. Interestingly, iPSC populations with perceived 'anomalies' can be coaxed to a more ESC-like cellular state either by continuous passaging--which attenuates these epigenetic differences--or treatment with small molecules that target the machinery responsible for remodelling the genome. This suggests that the establishment of an epigenetic status approximating an ESC counterpart is largely a passive process. The mechanisms responsible remain to be established. Meanwhile, other areas of reprogramming are rapidly evolving such as, trans-differentiation of one somatic cell type to another by the forced expression of key transcription factors. When it comes to assessing their practical usefulness, the same question will also apply.

Alternate JournalMol. Hum. Reprod.
PubMed ID21059705