Reprogramming Ordinary Skin Cells into iPSCs

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CRISPR iPSCs reprogramming using human skin cells expressing SOX2 and TRA-1-60, markers of human embryonic pluripotent stem cells

Recently, Timo Otonkoski’s team at the University of Helsinki, reprogrammed ordinary skin cells into iPSCs using CRISPR.

Their breakthrough builds on Shinya Yamanaka approach, known as “Yamanaka Factors.” Yamanaka used genes that can reprogram ordinary skin cells into iPSCs, induced pluripotent stem cells. That approach won the 2012 Nobel Prize in Physiology or Medicine.

The value of reprogramming ordinary skin cells into iPSCs is that, like stem cells, they can become any cell type in the body. This discovery transformed the field, opening new ways to study human disease and raising the possibility of treating conditions with a patient’s own cells.

CRISPR Reprogramming Ordinary Skin Cells into iPSCs

According to their study in Nature Communications, this is the first time researchers have fully reprogrammed mature human cells into pluripotent cells using only CRISPR. Instead of relying on the standard CRISPR system—where the CAS9 enzyme cuts DNA to disable genes—the team used a modified CAS9 that switches targeted genes on or off.

The Key: A Shared DNA Motif

Their success hinges on identifying a DNA sequence commonly found near genes involved in embryonic development. Because CAS9 must be guided to specific sites, this shared motif lets the researchers activate multiple pluripotency‑related genes in mature human skin cells, dramatically improving the efficiency of the reprogramming process.

A More Natural Path to Cell Fate

In a press release, Dr. Otonkoski emphasized the novelty and promise of this approach, noting that activating a cell’s own genes rather than overexpressing transgenes may offer a more natural and reliable way to control cell fate.

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