How brain stem cells move between resting and active states

Researchers from QIMR Berghofer and The Francis Crick Institute have discovered exactly how brain stem cells enter and exit a resting state called ‘quiescence’ — and their findings may lead to new approaches to brain health and cancer therapy.

Scientists previously believed that the neurons we are born with are all we ever have — but research over the past few years has shown that small populations of stem cells in the adult brain continue to generate new nerve cells throughout life, assisting us with memory and cognitive fitness. Most of the time, these brain stem cells exist in a hibernation-like state, lowering their metabolism to preserve themselves for when they are needed most. This resting state, known as quiescence, is an ancient biological strategy found across species in everything from yeast to humans, and in tissues ranging from muscle to blood.

Now, scientists have uncovered how brain stem cells shift between different depths of rest (akin to moving from deep sleep to light sleep) before becoming active again, and have mapped how these cells transition between states — a process that not only preserves the brain’s regenerative capacity but also primes it for repair when injury or disease strikes. Their work has been published in the journal Science Advances.

“This is the first time we’ve been able to show, in detail, how brain stem cells move between deep and shallow resting states and ultimately become active again,” said senior author Dr Lachlan Harris, from QIMR Berghofer. “Understanding this process is crucial, because it underpins how the brain repairs itself and stays resilient against neurodegenerative disorders. But it also may have profound implications for brain cancer, where tumour cells hijack this ancient resting program to evade therapies like chemotherapy and radiotherapy.”

Brain tumours, particularly aggressive types like glioblastoma, are notoriously difficult to treat in part because some cancer cells can also slip into this dormant state, becoming invisible to standard treatments that target active cancer cells. These ‘sleeping’ cancer cells can survive initial therapy, only to reactivate later and drive tumour recurrence — a key reason why brain cancers so often return after treatment.

The new research now opens the door to new therapeutic strategies. By learning how to manipulate the resting state in healthy brain stem cells, scientists hope to either wake up dormant cancer cells so they can be targeted by existing therapies or keep them asleep indefinitely to prevent tumour regrowth.

“This discovery is foundational because it doesn’t just advance our understanding of brain biology — it provides a roadmap for developing entirely new approaches to treating brain cancer or other neurological disease,” Harris said. “It’s a transformational step that builds on an ancient biological process, offering hope for tackling one of the most stubborn challenges in medicine.”

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