Basic principles for astrocyte-to-neuron conversion

Transcription factors have been employed to reprogram one type of cells into a different type of cells, an approach commonly called cell transdifferentiation. Astrocyte-to-neuron conversion is one type of cell transdifferentiation, where neural transcription factors are overexpressed in astrocytes to convert them into neurons. Many neural transcription factors, such as NeuroD1, Ascl1, Ngn2 and various combinations, have been demonstrated to successfully convert astrocytes into neurons both in vitro and in vivo, opening a new avenue for neural regeneration using internal glial cells. While significant progress has been made using in vivo astrocyte-to-neuron conversion approach to regenerate functional new neurons and repair damaged neural circuits, challenges also arise regarding how to identify genuine cell conversion. Here, I review critical steps during astrocyte-to-neuron conversion process, from initial expression of neural transcription factors in astrocytic nuclei to transitional stage in-between astrocytes and neurons, and eventual acquisition of mature neuronal properties. This review provides a general guideline on how to identify genuine astrocyte-to-neuron conversion with comprehensive approaches.