How can a skin cell become a nerve cell?

Abstract

How can a skin cell become a nerve cell? This is one of the 125 big questions raised in Science magazine for its 125th anniversary. Here we summarize what we know on this subject. In particular, we discuss recent success in converting fibroblasts, one of the common cells found in skin, into nerve cells including neuron. Despite these successes in making nerve cells of skin cells in laboratory, it is quite challenging in translating these breakthroughs into success in clinic. The nervous system includes the central nervous system, the peripheral nervous system and the autonomic nervous system. Many insults, including infection, poisoning, immune damage, nutritional disorders, endocrine disorders and genetic factors, may damage the nervous system such that nerve cells undergo degeneration, apoptosis, or necrosis, leading to neurological impairments. The impairments in peripheral nerve system may be repaired without much defects with skilled microsurgical techniques. However, options are quite limited in repair lesions in the central nerve system as it was known that neurons in the central nervous system (CNS) could not regenerate after damage and would only be replaced by glial cells. Neuronal stem cells hold great promise in repairing lesions in the nerve systems. While embryonic stem cells may be complicated with ethical issues, adult stem cells such as neuronal stem cells are difficult to isolate and purify, with limited differentiation capacity. One solution is the induction of neuronal cells from skin fibroblast directly. Indeed, in 2010, Vierbuchen et la use three transcription factors, Ascl1 , Brn2/4 and Myt1L (ABM), to directly convert fibroblasts into induced neurons (iNs). Because fibroblasts are easy to obtain, they have become the first choice of the initial cells to induce nerve cells. This technology has become an active area of research in recent years. Going forward, it is possible to apply many similar strategies including transcription factors, small molecules, microRNAs to the induction of neuron, glial cell, astrocyte oligodendrocyte and Schwann cells from fibroblast. The cells generated from these strategies can be used to treat Parkinson′s disease and Amyotrophic lateral sclerosis. There is a bright future for the generation of nerve cells from skin cells. In deed, similar approaches have been attempted in animal models. For human therapy, we must perform more safety tests, improve efficiency and enhance survival rate. Therefore, we need a lot of work done in clinical practice. Most importantly, the investigation of nerve cell generation from skin fibroblast may help us to understand the basic rules and laws of cell fate determination and the mechanism for human developments. Current work is laying a solid foundation for the development of therapies.