Cellular Metamorphosis

Researchers from the University of Michigan, University of Maryland, and Harvard University have developed a method of making cells undergo a remarkable transformation: a shortcut that can transform skin cells into any other type. Their study detailing this metamorphosis was recently published in the Proceedings of the National Academy of Sciences (PNAS).

"Cells in our body naturally specialize," said senior author Indika Rajapakse, a professor in mathematics and bioinformatics at University of Michigan, in a press release. "What we propose could provide a shortcut to doing the same, to help any cell become a targeted cell type."

The new method builds on a technique pioneered in the late 1980s, which bathes cells in transcription factors (TFs), molecules that encourage genes to "read" the DNA of certain cells. Rajapakse's team revised the method by targeting cells with specific TFs at certain points in their growth, using a mathematical control model to map out the proper timing for each TF injection.

By tracking when certain genes are "read," the team could understand when and how certain transcription factors act in transforming a cell.

"We believe we can go from the cell's initial configuration to the desired configuration," says Rajapakse.

Skin Cells: The Future of Medicine

The team is now testing this method with the help of Max Wicha, the Forbes Professor of Oncology at Michigan Medicine.

"This algorithm provides a blueprint that has important implications for cancer, in that we think cancer stem cells may arise from normal stem cells via similar reprogramming pathways," says Wicha, co-author of the paper. "This work also has important implications for regenerative medicine and tissue engineering, since it provides a blueprint for generating any desired cell type."

Similar work in stem cells has opened incredible new doors for medicine, allowing doctors to create customized treatments, grow complex structures like neurons, and cure seemingly intractable diseases like cancer and diabetes. The discovery of stem cell pluripotency — their ability to transform into any other cell type — earned John B. Gurdon and Shinya Yamanaka the Nobel Prize in medicine in 2012.

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For many years, the use of stem cells has been highly controversial, as early methods required that the cells be removed from human embryos. Yet that period appears to be ending: research into new methods of harvesting stem cells, as well as work like that of the U. Mich, U. Maryland, and Harvard team that requires nothing more than a skin scrape, could usher in a new era of non-invasive, highly flexible customized medicine for a range of illnesses.

As Wicha added, this work "also demonstrates the beauty of combining mathematics and biology to unravel the mysteries of nature."

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