by King’s College London

Astroglial origin of the vast majority of Ascl1SA6-Bcl2 iNs. Credit: Science Advances (2024). DOI: 10.1126/sciadv.adl5935

Researchers have successfully demonstrated how astroglia—cells that support the functioning of the brain—can be reprogrammed into cells resembling interneurons.

The research, published in Science Advances, represents not only an important step forward in neuronal engineering, but also has vital implications for regenerative medicine, which researchers hope could be used to restore dysfunctional brain circuits like those seen in people with epilepsy.

Working with mice shortly after birth, researchers coaxed astroglia to synthesize a protein, Ascl1, that plays a key role in the development of the nervous system. They found that when mutated, Ascl1 became highly efficient in converting astroglia into functioning neurons, much more so than the form of the protein that is generated naturally by the body.

“While the neurons we induced differ from those the body creates itself, we’re excited to show that engineered neurons can acquire highly specific properties. Our findings will allow us to further close the gap between induced and endogenous neurons and thereby render them ever more useful for future translation in regenerative medicine,” says Professor Benedikt Berninger, Professor of Developmental Neurobiology at King’s IoPPN and the study’s senior author.

The research team found that the neurons they generated displayed properties that were similar to those native to the brains they were working on, including the ability to fire at very high frequencies, a telltale hallmark of a particular class of interneurons that play a vital role in regulating brain circuitry.

Dr. Nicolás Marichal, Research Associate at the Centre for Developmental Neurobiology at King’s IoPPN and one of the study’s lead authors said, “This landmark study’s success in creating neurons from astroglia breaks new ground in regenerative medicine, offering promise for the restoration of aberrant circuitry and brain function in neurological conditions. This work paves the way for further research to exploit these findings and leverage lineage reprogramming of glia into subtype specific neurons as a new therapeutic avenue.”

More information: Nicolás Marichal et al, Reprogramming astroglia into neurons with hallmarks of fast-spiking parvalbumin-positive interneurons by phospho-site–deficient Ascl1, Science Advances (2024). DOI: 10.1126/sciadv.adl5935

Journal information:Science Advances

Provided by King’s College London