Lineage reprogramming of glia into subtype-specific cortical neurons

The cerebral cortex is the seat of higher cognitive functions but is often severely affected by disease or trauma. We will assess the potential for a novel strategy of cell-based therapy, involving the cell fate conversion of brain cells other than nerve cells into induced neurons. The underlying idea is that the brain harbours many so-called glial cells which have been shown to be amenable to a cell fate conversion into induced neurons in vitro. This can be achieved by forced expression of proteins that regulate cell fate decisions during development. Recent work also suggests that this might be possible in vivo and we want to rigorously scrutinise this possibility.

We aim to convert glial cells into local inhibitory neurons (interneurons) of the cerebral cortex as these cells are often afflicted in neurological and neuropsychiatric disorders. Induced neurons will be closely compared with endogenous neurons found in the brain. While many of the experiments will be conducted with mouse cells, we will expand the scope of our study by testing the possibility of converting human glia into induced neurons as a prerequisite for future translation into cell-based therapies.

The findings will inform investigations into cell-based therapies.