New research from the lab of Jian Feng, Ph.D., at the University at Buffalo (SUNY), defines an improved method to produce neurons directly from skin cells. Neurons, or nerve cells, are affected by a number of different degenerative diseases. In Parkinson’s disease, for example, neurons that produce the neurotransmitter dopamine are lost. However, studying human neurons in the lab has long been difficult because of lack of access to patient tissues. Researchers can generate many different types of neurons from embryonic stem cells in the lab, but these cells tend to be immature. In the past few years, scientists have taken a new approach by converting easily obtainable skin cells directly into neurons. This approach provides three advantages: the cells can be generated for individual patients, the cells are more mature than stem cell-derived neurons, and the process is much quicker than deriving neurons from stem cells. However, the process is also highly inefficient. Dr. Feng’s group identified barriers to the conversion process, and now reports in Nature Communications on means to overcome them, significantly improving the efficiency of generation of dopamine-producing neurons. The first barrier to conversion is p53, a tumor suppressor, which helps maintain the skin cells’ identity. The second barrier is cell division; actively dividing cells are difficult to convert to other cell types. Combining suppression of p53 activity and stopping the cell cycle, plus tweaks to the liquid medium the cells are grown in, with an older method caused the skin cells to convert to dopamine neurons within a couple of days, and with efficiencies approaching 100% from a previously established fetal cell line. Even using cells from aged patients (96 years in one case), yielded efficiencies of nearly 50%, well beyond prior methodologies. If these same approaches can be applied to generation of other cell types, researchers will soon have greater access to otherwise rare cell types, allowing better disease modeling in the most relevant cells, those from humans. This research was funded in part by NYSTEM contracts C028129 and C029556 to Dr. Feng, as well as a NYSTEM shared facility contract, C026714, to the University at Buffalo.
Jiang H, Zu Z, Zhong P, Ren Y, Liang G, Schilling HA, Hu Z, Zhang Y, Wang X, Chen S, Yan Z, Feng J. Cell Cycle and p53 Gate the Direct Conversion of Human Fibroblasts to Dopaminergic Neurons. Nature Communications. 2015 Dec 7;6.