Figure 2. Theoretical ways of generating new neurons via reprogramming in vivo.

Within the multicellular, complex environment of the adult CNS, astrocytes and other resident cell types, like pericytes, may be instructed to convert into plastic cellular intermediates (e.g. neuroblasts), which in turn may be receptive to instructive signals and become neurons. Neurons may transition to a more plastic cell state by undergoing epigenetic remodeling, which in turn could make them more permissive to fate specifying transcription factors able to induce the acquisition of a new neuronal class-specific identity. They also could revert to a more plastic cellular intermediate (e.g. neural stem cells, neuroblasts etc.). An alternative route to neuronal replacement could include the scenario of neuronal cell division. This process may also contribute to reset some of the epigenetic barriers normally blocking reprogramming.