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A Better Way to Discriminate iPSCs vs ESCs

Image credit: <a href=First of all, a hearty congratulations to Dr. Shinya Yamanaka and Dr. John Gurdon for winning this year’s Nobel prize for Medicine, for their discoveries that adult cells could be transformed back to embryonic-like states. Recently, Dr. Yamanaka has publicly warned of dangerous “stem cell therapies” currently offered in various countries, without any pre-clinical testing in animals. This was an important message considering possible tragedies, both for any patients desperate for a cure, who end up sick or dead…and for the public, who might lose their trust in potential future stem cell therapies developed safely under strict scientific methods.

Induced pluripotent stem cells (iPSCs) can be transformed from somatic cells, through the expression of only four transcription factors, using Kyoto University viral delivery methods. However, its been shown that the process of reprogramming these cells results in genetic and epigenetic aberrations in comparison to embryonic or parental somatic cells. Other methods also have been developed, or are in development, to produce IPSCs. For example protein-induced pluripotent stem cells. Goals for any method include producing non-tumorigenic, completely reprogrammed cells

For the recent pub, Sergio Ruiz & Dinh Diep et al. Identification of a specific reprogramming-associated epigenetic signature in human induced pluripotent stem cells. (2012) PNAS, the authors developed a method to discriminate between hESCs and hiPSCs based on targeted bisulfite sequencing with padlock probes, to produce unbiased hierarchical clustering of global methylation. Interestingly, higher reprogramming efficiency was associated with less difference in methylated CpG sites between somatic and iPSC cells. Methylation changes at only nine genes amongst all the iPSC cell lines, regardless of origin cell type. The epigenetic signature for segregation was made clear because areas of lower CgP content were covered. Previous analysis by restricted representation bisulfite sequencing (RRBS), which focuses on CpG islands, could not differentiate between ESCs and iPSCs in this way. The caveat is that more cell lines need to be tested to enhance this epigenetic signature’s utility.

Ruiz S, Diep D, Gore A, Panopoulos AD, Montserrat N, Plongthongkum N, Kumar S, Fung HL, Giorgetti A, Bilic J, Batchelder EM, Zaehres H, Kan NG, Schöler HR, Mercola M, Zhang K, & Izpisua Belmonte JC (2012). Identification of a specific reprogramming-associated epigenetic signature in human induced pluripotent stem cells. Proceedings of the National Academy of Sciences of the United States of America, 109 (40), 16196-201 PMID: 22991473

This entry was posted in Cellular Biology, DNA Methylation, Reduced representation bisulfite sequencing, Regenerative Medicine, Stem Cells and tagged , , , . Bookmark the permalink.

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