Faculty Opinions recommendation of Epigenetic memory in induced pluripotent stem cells.

To date biomedicine and pharmacology have required generating new and more consummate models. One of the most perspective trends in this field is using induced pluripotent stem cells (iPSCs). iPSC application requires careful high-throughput analysis at the molecular, epigenetic, and functional levels. The methods used have revealed that the expression pattern of genes and microRNA, DNA methylation, as well as the set and pattern of covalent histone modifications in iPSCs, are very similar to those in embryonic stem cells. Nevertheless, iPSCs have been shown to possess some specific features that can be acquired during the reprogramming process or are remnants of epigenomes and transcriptomes of the donor tissue. These residual signatures of epigenomes and transcriptomes of the somatic tissue of origin were termed epigenetic memory. In this review, we discuss the epigenetic memory phenomenon in the context of the reprogramming process, its influence on iPSC properties, and the possibilities of its application in cell technologies.

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PO141 PREFERENTIAL EXPRESSION OF LIVER SPECIFIC GENES AND EPIGENETIC MEMORY OF INDUCED PLURIPOTENT STEM CELLS DERIVED FROM MOUSE EXOCRINE PANCREAS

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(14)70435-8 ◽

2014 ◽

Vol 106 ◽

pp. S119

Author(s):

K. Minami ◽

D. Nukaya ◽

R. Hoshikawa ◽

N. Yokoi ◽

S. Seino

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Exocrine Pancreas ◽

Epigenetic Memory ◽

Preferential Expression ◽

Induced Pluripotent

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Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1608679113 ◽

2016 ◽

Vol 113 (43) ◽

pp. 12202-12207 ◽

Cited By ~ 82

Author(s):

Timothy Alexander Hore ◽

Ferdinand von Meyenn ◽

Mirunalini Ravichandran ◽

Martin Bachman ◽

Gabriella Ficz ◽

...

Keyword(s):

Dna Methylation ◽

Stem Cells ◽

Retinoic Acid ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Embryonic Stem ◽

Epigenetic Memory ◽

Mechanistic Insight ◽

Induced Pluripotent ◽

Tet Enzymes

Epigenetic memory, in particular DNA methylation, is established during development in differentiating cells and must be erased to create naïve (induced) pluripotent stem cells. The ten-eleven translocation (TET) enzymes can catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidized derivatives, thereby actively removing this memory. Nevertheless, the mechanism by which the TET enzymes are regulated, and the extent to which they can be manipulated, are poorly understood. Here we report that retinoic acid (RA) or retinol (vitamin A) and ascorbate (vitamin C) act as modulators of TET levels and activity. RA or retinol enhances 5hmC production in naïve embryonic stem cells by activation of TET2 and TET3 transcription, whereas ascorbate potentiates TET activity and 5hmC production through enhanced Fe2+ recycling, and not as a cofactor as reported previously. We find that both ascorbate and RA or retinol promote the derivation of induced pluripotent stem cells synergistically and enhance the erasure of epigenetic memory. This mechanistic insight has significance for the development of cell treatments for regenenerative medicine, and enhances our understanding of how intrinsic and extrinsic signals shape the epigenome.

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