Direct Conversion of Somatic Cells into Induced Neurons

The progressive loss and degeneration of neurons in the central nervous system (CNS), as a result of traumas or diseases including Alzheimer's, Parkinson's, Huntington's disease, stroke, and traumatic injury to the brain and spinal cord, can usually have devastating effects on quality of life. The current strategies available for treatments are described including drug delivery, surgery, electrical stimulation, and cell-based tissue engineering approaches. However, apart from cell-based therapy, other attempts are limited in improving clinical outcomes. Recently, stem cell and neural stem cell (NSC) in particular therapy has been proposed as an attractive and promising strategy for regenerative medicine due to their unique biological attributes, such as giving rise to neuronal lineage commitment in accordance with the neural development. Nevertheless, stem cell strategy still faces numerous challenges, including ethical issue, tumor formation, and graft rejection. Thus, seeking a more appropriate approach like direct reprogramming or lineage reprogramming is critical. Compared to induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), direct lineage reprogramming of somatic cells to generate induced neurons (iNs) without undergoing a state of pluripotent still has several advantages such as short induction cycle, high transdifferentiation efficiency, no ethical concerns, and risk of neoplasia. On the basis of these advantages, cell reprogramming will hold great promise for therapeutic cell replacement, disease modeling establishment, drug screening, and personalized medicine. Here, we systematically review recent advances in somatic lineage reprogramming into iNs, including the identification of novel reprogramming factors, the underlying molecular mechanisms and the concerns exist, as well as the major challenges in the future.