CRISPR Approach Converts Skin Cells into Pluripotent Stem Cells

CRISPRa reprogrammed induced pluripotent stem cell colonies stained for pluripotency marker expression. (Credit: Otonkoski Lab/ University of Helsinki)

Researchers have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell’s own genes, using gene editing technology CRISPRa. 

Up until now, reprogramming has only been possible by introducing the critical genes for the conversion, called Yamanaka factors, artificially into skin cells where they are not normally active at all. 

This was achieved by using gene editing technology CRISPRa, that can be directed to activate genes. 

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The method utilises a blunted version of the Cas9 gene scissors that does not cut DNA, and can therefore be used to activate gene expression without mutating the genome.

“Reprogramming based on activation of endogenous genes rather than overexpression of transgenes is [also] theoretically a more physiological way of controlling cell fate and may result in more normal cells,” said Professor Timo Otonkoski of the University of Helsinki. 

“In this study, we show that it is possible to engineer a CRISPR activator system that allows robust reprogramming of iPSC,” he adds. 

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An important key for the success was also activating critical genetic element that was earlier found to regulate the earliest steps of human embryo development after fertilisation.

“Using this technology, pluripotent stem cells were obtained that resembled very closely typical early embryonal cells,” said Professor Juha Kere of Karolinska Institutet and King’s College London. 

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The discovery also suggests that it might be possible to improve many other reprogramming tasks by addressing genetic elements typical of the intended target cell type. 

“The technology may find practical use in biobanking and many other tissue technology applications,” said PhD student, Jere Weltner, who is first author of the study, published in Nature Communications. 

“In addition, the study opens up new insights into the mechanisms controlling early embryonic gene activation.” 

 


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