21/10/24
The Berninger lab, in partnership with their international collaborators, have made a pioneering and exciting discovery in neural regeneration. Their findings, published in Science Advances, demonstrate how astroglia, brain support cells, can be reprogrammed into authentic, functioning neurons that exhibit characteristics of fast-spiking parvalbumin-positive interneurons. Nicolás Marichal, Sophie Péron, Ana Beltrán Arranz et al.’s innovative approach not only represents an advancement in neuronal engineering but has important implications for regenerative medicine and restoring dysfunctional brain circuits.
The team, led by Professor Benedikt Berninger, found that by using a mutated version of the Ascl1 transcription factor, known as Ascl1SA6, in combination with the protein Bcl2, they could efficiently convert astroglia in the early postnatal mouse cortex into induced neurons. Ascl1SA6, designed to enhance neurogenic activity by altering specific phospho-acceptor sites, demonstrated a significant improvement in converting astroglia into mature, functional neurons capable of high-frequency firing.
Marichal, Péron, Beltrán Arranz et al.’s work is especially exciting as it addresses previous limitations in converting glial cells to neurons in vivo. The neurons generated displayed molecular and electrophysiological properties similar to native cortical interneurons, including the ability to fire at high frequencies, a telltale hallmark of fast-spiking parvalbumin-positive interneurons. These neurons play a vital role in regulating brain circuitry and are implicated in various neurological conditions, including epilepsy and schizophrenia.
“While these induced neurons are still different from their endogenous counterparts, we are excited to learn 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.” Professor Benedikt Berninger.
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. Marichal, Péron, Beltrán Arranz et al.’s 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.
Nicolás Marichal, Sophie Péron, and Ana Beltrán Arranz contributed equally to this work. The original article is available via Science Advances
