The human body has powerful healing abilities. But treating brain disorders is no easy task, as brain cells neurons have limited ability to regenerate. Nonetheless, stem cells are a form of natural backup; a vestige of our days as still-developing embryos. The difficulty is that with age; neural stem cells ‘fall asleep’ and become harder to when repairs are needs. Despite efforts to harness these cells to treat neurological damage; scientists have until recently been unsuccessful in decoding the underlying ‘sleep’ mechanism.
Neural stem cells
Now, researchers at Kyoto University studying brain chemistry have revealed the ebb and flow of gene expression that may wake neural stem cells from their slumber. These findings, which may also apply to stem cells elsewhere in the body, were recently published in the journal Genes & Development. “No one before us has directly compared active stem cells in embryos with inactive, who points out that at least two genes and their associated proteins regulating activation had already identified.
The team focused their attention on protein ‘He’s1’; which is strongly expressing in the adult cells. This normally suppresses the production of other proteins such as ‘Ascl1’, small amounts of which are periodically producing by active stem cells. Monitoring the production of the two proteins over time, the team pinpointed a wave-like pattern that leads to stem cells waking up and turning into neurons in the brain.
The regulatory mechanisms
When they knocked out the genetic code needed to make Hes1; the cells started to make more Ascl1; which then 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. 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.”
The molecular nature of differences between the active and quiescent states of stem cells is not fully understood. Notch signaling is reportedly required to maintain both active and quiescent neural stem cells; but how the same signaling pathway regulates such different states of neural stem cells remained to determined. Here, they found that expression of the Notch signaling effector Hes1 oscillates in active neural stem cells; but is high in quiescent neural stem cells. The ascl1 expression also oscillates in active neural stem cells due to periodic repression by Hes1, while it is suppressed in quiescent neural stem cells by high Hes1 expression.