Scientists Use CRISPR to Convert Skin Cells into Pluripotent Stem Cells

Scientists Use CRISPR to Convert Skin Cells into Pluripotent Stem Cells

Researchers at the Otonkoski Lab at the University of Helsinki, the Karolinska Institute, and King’s College London are the first to successfully convert human skin cells into induced pluripotent stem cells (iPSCs) using the cells’ own genes.

Previously, the process has only been possible by introducing new genes. These genes are known as Yamanaka factors, taking their name from the Nobel prize-winning Japanese scientist Shinya Yamanaka who made the discovery.

The researchers were able to get the cells’ own genes to reprogram the cells using a version of the CRISPR gene editing system. CRISPR is a gene editing tool that allows scientists to make highly specific cuts to DNA. Guide RNA is used to identify a specific sequence of DNA and an enzyme, usually Cas9, is used to make the cut to either remove a defective gene or insert new genetic material.

In this case, CRISPR-Cas9-based gene activation (CRISPRa) is used. This is the same gene editing tool, but it lacks the ability to cut the DNA. Instead, the system is used to activate genes rather than remove them. This system allows multiple genes to be targeted and activated at the same time.

The researchers report that they have achieved successful “reprogramming of primary human skin fibroblasts into induced pluripotent stem cells (iPSCs) using CRISPRa, targeting endogenous OCT4, SOX2, KLF4, MYC, and LIN28A promoters.”

An important element of the process was the activation of a critical genetic element that had been earlier discovered to regulate the earliest steps of human embryo development after fertilization.

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

The pluripotent stem cells obtained using CRISPRa very closely resembled typical early embryonal cells. The researchers note that this technology could be valuable in bio banking and many other tissue technology applications, promoting far more efficient and specific reprogramming of human cells.

The research is detailed in the paper – Human Pluripotent Reprogramming with CRISPR Activators – which was recently published in the journal Nature Communications: 9, Article No. 2643

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