Reprogramming Skin Cells into Neural Stem Cells By Introducing One Gene


Transforming skin cells into nerve cells that interconnect and send nerve impulses to each other requires an extensive amount of reprogramming. The production of induced pluripotent stem cells is rather labor-intensive and introduces some risks. However, a new procedure designed by Yadong Huang at the Gladstone Institutes has shown that the introduction of a single gene into skin cell can generate nerve cells from skin cells.

This single gene, Sox2, transforms skin cells within days into early-stage brain stem cells known as induced neural stem cells or iNSCs. In culture, iNSCs self-renew and mature into neurons that can connect with each other and then transmit electro-chemical signals between each other. When the iNSCs were cultured for one month, they had already formed a completely new neural network.

An excited Huang made these points: “Many drug candidates, especially those developed for neurodegenerative diseases, fail in clinical trials because current models don’t accurately predict the drug’s effects on the human brain. Human neurons derived from reengineered skin cells could help assess the efficacy and safety of these drugs, thereby reducing risks and resources associated with human trials.”

Huang’s findings build on the work of Japanese research Shinya Yamanaka, who was the first scientist to publish the production of induced pluripotent stem cells. Since that time, other researchers have used genetic engineering techniques to directly reprogram adult cells into other types of adult cells without passing through the embryonic-stem-cell stage. Last year, Sheng Ding managed to use a combination of small molecules and genes to transform skin cells directly into neural stem cells. Huang’s technique now simplifies this technique even more so that only one gene is required to reprogram skin cells into neural stem cells. By avoiding the induced pluripotent stem cell stage, Huang and Ding hope to avoid the risk of tumor formation and the mutations induced by the production of induced pluripotent stem cells.

Karen Ring, a graduate student in Biomedical Sciences at the University of California, San Francisco, who was the lead author on this paper vouched for the safety of the iNSCs: “We wanted to see whether these newly generated neurons could result in tumor growth after transplanting them into mouse brains. Instead, we saw the reprogrammed cells integrate into the mouse’s brain, and not a single tumor developed.”

Huang’s paper also addresses the function Sox2 in the reprogramming of the skin cells. Huang and his research team also want to identify similar regulators that direct the development of specific types of neurons in the brain that tend to degenerate in the case of particular types of neurodegenerative diseases. Huang noted: “If we can pinpoint which genes control the development of each neuron type, we can generate them in the Petri dish from a single sample of human skin cells. We could then test drugs that affect different neuron types, such as those involved in Parkinson’s disease.” Huang added that such a discovery would help drug developers design treatments for neurodegenerative diseases that are much more specific, and the drug design would probably occur much faster.

Alzheimer’s disease still afflicts 5.4 million people in the US alone and this number is thought to triple by 2050. There are still no medications that can reverse the devastation wrought by this disease. Huang’s data might provide the means to test such new drugs.

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mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).