For all its profound cognitive capabilities, the human brain fails at a relatively mundane task: repairing itself. Though it contains stem cells, which could theoretically produce multiple kinds of specialized cells for as long as an organism lives, most neural stem cells remain in an inactive state, known as quiescence, throughout adulthood. A new study investigated how to quickly reactivate these “sleeping” neural stem cells, laying the groundwork for the possible future production of new neurons that could help the brain recover from injury and disease.
Quiescent neural stem cells were thought to be arrested in the so-called G0 phase of the cell cycle, which represents the lowest level of preparedness for division into new cells. When Andrea Brand, a professor of molecular biology at the University of Cambridge, and her doctoral student Leo Otsuki investigated the quiescence of neural stem cells in fruit flies (Drosophila melanogaster), they discovered that three-quarters of quiescent neural stem cells had already advanced to G2, the last phase before cell division. “G2 stem cells are thus poised and ‘ready to go’,” said Brand. “Speed is important in a regenerative context,” Brand added, “which is why we are very excited about G2 quiescent stem cells.” Prior to this finding, G2 quiescent stem cells had never been reported in fruit flies or mammals.
The researchers began studying the neural genetics of fruit flies and isolated a gene called tribbles (trbl), which deactivates and maintains G2 cells in prolonged quiescence. Identifying the role of trbl in quiescence makes it a promising target for future therapeutic research. Drugs that block the mechanism of trbl could reawaken quiescent neural stem cells, which could open up new treatment avenues for neurodegenerative diseases, such as Alzheimer’s, or brain tissue damaged by strokes and head trauma. Further regenerative possibilities may exist: “Having identified G2 quiescent stem cells,” Brand said, “we can begin to look for them in other tissues around the body, not just in the brain.” (Science)