Novel research moves us closer to unlocking the brain’s regenerative potential

Written by Mike Gregg

Researchers at Kyoto University have discovered that ‘waves’ of Hes1 and Ascl1 gene expression are responsible for controlling the active state of adult neural stem cells.

Treating brain disorders continues to be a challenging task as neurons have very limited ability to regenerate. The aging process causes further problems as brain stem cells in older patients become dormant and are very difficult to ‘wake up’ when repairs are required.

Novel research carried out by researchers from Kyoto University (Kyoto, Japan) has highlighted that specific gene expression is linked to the neural stem cells’ dormancy. They have revealed that at least two genes and their associated proteins are responsible for regulating the activation of the neural stem cells.

The protein involved in regulating the activity of neural stem cells, Hes1, is strongly expressed in adult cells and inhibits the production of other proteins such as Ascl1. To establish how these proteins influenced the stem cells, the researchers monitored the production of these proteins over time. They found that a wave-like pattern resulted in the neural stem cells becoming active and differentiating into neurons in the brain.

The research also identified that when the Hes1 gene is ‘knocked out’, the cells produced more Ascl1 protein which activated almost all the neural stem cells.

“It is key that the same genes are responsible for both the active and quiescent states of these stem cells, only the expression dynamics differ between the two,” explained group leader Ryoichiro Kageyama (Kyoto University).

“A better understanding of the regulatory mechanisms of these different expression dynamics could allow us to switch the dormant cells on as part of a treatment for a range of neurological disorders,” concluded Kageyama.

Source: Sueda R, Imayoshi I, Harima Y, Kageyama R. High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain. Genes Dev. 2019; 33 (9-10): 511.