Glia-to-neuron reprogramming to the rescue?

Jack W.Hickmott; Cindi M.Morshead

doi:10.4103/NRR.NRR-D-24-00281

Abstract：Over the last two decades, the dogma that cell fate is immutable has been increasingly challenged, with important implications for regenerative medicine. The breakthrough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed. An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogramming hypothesis - that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state. A significant body of evidence demonstrates direct cellular reprogramming in vitro (Vasan et al., 2021; Bocchi et al., 2022) and an exciting application of this technology is the use of direct cellular reprogramming in vivo. Indeed, the promise of direct cellular reprogramming to replace lost cells in the central nervous system following neurotrauma or neurodegenerative disease is remarkable. Here we will discuss the hope, the hype, and the scrutiny that surrounds the promise of direct cellular reprogramming, specifically related to the generation of induced neurons from glial cells in vivo. We will highlight successes in the field, examine criticisms of this body of literature, and draw on previous examples of scientific controversy to propose a path forward to "rescue" the field.