AsianScientist (Aug. 8, 2017) – Researchers at the Duke-NUS Medical School have found proteins that can reactivate neural stem cells (NSCs). Their findings, published in Nature Communications, could lead to stem cell-based therapies for neurodevelopmental and neurodegenerative disorders such as microcephaly and Alzheimer’s disease.
Only a small fraction of NSCs in adult mammalian brains is proliferative; most NSCs are in a non-dividing state also known as quiescence. The balance between NSC proliferation and quiescence is essential for brain development and emerging evidence suggest that its imbalance is linked to neurodevelopmental disorders, such as microcephaly.
On the other hand, the population of quiescent NSCs in the brain increases with aging, which is associated with declining brain function. Understanding how endogenous NSCs can be activated has huge potential in regenerative medicine. However, it is poorly understood how NSCs switch between proliferation and quiescence in vivo.
In the present study, researchers used fruit flies (Drosophila melanogaster) to show that proteins in the spindle matrix complex play an essential role in controlling gene expression during NSC reactivation. In particular, they found that a protein called chromator (Chro) is not only critical for NSC reactivation, but is also essential for preventing re-entry into inactivation.
The team employed state-of-art genomic technique for transcriptome analysis in vivo and identified binding-sites of Chro in NSCs. The main findings from these experiments suggest that Chro is a master nuclear factor that reactivates NSCs through regulating gene expression of key transcription factors that either promote or repress the proliferation of NSCs. The study also suggests that Chro functions downstream of Insulin/PI3k pathway, which is known to promote NSC reactivation and mutations of which are found in microcephalic patients.
“It may be in its early stage, but this should help to open up avenues for further research and the development of potent therapies for neurodevelopmental disorders in the future,” said lead author Wang Hongyan, an Associate Professor and Deputy Director of Duke-NUS’ Neuroscience and Behavioural Disorders Programme.
The article can be found at: Li et al. (2017) An Intrinsic Mechanism Controls Reactivation of Neural Stem Cells by Spindle Matrix Proteins.
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Source: Duke-NUS Medical School; Photo: Shutterstock.
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