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Madison — Researchers at the University of Wisconsin-Madison have developed a novel strategy to reprogram cells from one type to another in a more efficient and less biased manner than previous methods.

The ability to convert cells from one type to another holds great promise for engineering cells and tissues for therapeutic application, and the new Wisconsin study could help speed research and bring the technology to the clinic faster.

The new approach, published this week (Dec. 5, 2016) in the Proceedings of the National Academy of Sciences (PNAS), uses a library of artificial transcription factors to switch on genes that convert cells from one type to another. Natural transcription factors are cellular molecules that bind to DNA to turn genes on and off. They help determine cell fate, meaning that if a cell is destined to be a skin cell, a heart cell or an eye cell, different transcription factors switch on specific sets of genes that program the cell to attain one state or another.

Using artificial transcription factors made in the lab, researchers are trying to find which ones best mimic these natural changes in cell fate.

"Our interest in changing cell fate comes from understanding how cells selectively use the information in our genomes to make specific cell types and also from the many therapeutic benefits such knowledge can offer," said Asuka Eguchi, the study's lead author and a member of Professor Aseem Ansari's lab in the UW-Madison Department of Biochemistry. "For example, if a patient needs a certain cell type, the idea is we can reprogram their own cells to what they need, rather than relying on donor cells. This allows us to study patient-specific cells and potentially avoids issues with immune response where a patient's body could reject the cells."

"Generating these pluripotent stem cells also helps us avoid having to make embryonic stem cells, which can be controversial," says Eguchi, who is a recent graduate of the UW-Madison Cellular and Molecular Biology Training Program. "We can also start better investigating direct conversions, which are conversions from one cell type to another without the need to go to the pluripotent stage first because that can cause problems in some contexts. This tool opens up the doors to research these areas more effectively."

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