Direct reprogramming or cell-fate conversion across cell lineages emerges as an innovative approach toward cell-based therapies for regenerative medicine. In the CNS, direct lineage reprogramming of non-neuronal cells into clinically relevant neurons represents a highly innovative strategy to regenerate lost neurons for brain repair in several neurological disorders (for review see Heinrich et al., Nature Cell Biol, 2015 and Vignoles et al., Trends Mol Med, 2019). Along this line, we contributed important work by demonstrating that mouse astroglia can be directly reprogrammed in vitro to generate functional induced neurons (iNs) with different neurotransmitter identity (Heinrich et al., 2010; Heinrich et al., 2011). A major challenge was the translation of these findings obtained in the culture dish into the context of the adult brain in vivo. We showed that NG2 glia can be converted into iNs in the adult mouse cortex in vivo and following acute invasive injury (Heinrich et al., 2014).

Based on these studies our current research aims now at reprogramming glial cells residing within the injured brain –in pathological conditions– into functional iNs that:

• Acquire the same molecular identity and phenotype as lost neurons
• Functionally integrate into endogenous neuronal networks
• Modulate the pathological network activity with beneficial effects.