Anchors away! When neural stem cells decide a change is as good as a rest

Neural stem cells are anchored to their niche until they
decide to migrate.
Painting: 'Canada Timber Docks, Liverpool.
Towards close of day' by Robert Dudley (active 1865-1891)

Between 1830 and 1930, over nine million people left England from Liverpool  on ships bound for Australia, Canada and America. The Merseyside port swelled with would-be emigrants, all holding tightly to the decision to leave their homes for the promise of a new life.

Stem cells in the brain are similarly destined for change. A recent study suggests their transformation into specialised cells, a process known as differentiation, is combined with the decision to migrate to where they are needed, bringing new understanding of the development and repair of brain tissue.

In the brain, neural stem cells (NSCs) can be found anchored in  'niches': port-like microenvironments which shelter the cells in a dormant, undifferentiated state. NSCs might eventually migrate all over the brain, some becoming neurons along the way, but this can only happen correctly if differentiation is timed precisely with release from the niche.

In a paper published recently in Nature Cell BIology, Francesco Niola and colleagues found the same set of proteins inside a neural stem controls both anchorage to the niche and the onset of differentiation, synchronising the two processes. This control may prevent differentiation from misfiring, leading to problems in development or even cancer.

Neural stem cells migrate to different parts of the brain, becoming different
types of brain cell such as neurons.
Painting: 'Ship off Liverpool', Robert Salmon (1811)

The team from Colombia University, New York looked inside mouse NSCs. They found that Inhibitor of DNA-binding (Id) proteins prevent an NSC from differentiating too soon by repressing the transcription of certain genes. Id proteins were also found to control RAP1, a protein involved in adhesion between the stem cell and its niche.

Dr Anna Lasorella, a senior author of this paper said a key question for the future was to, "determine whether Id proteins also maintain stem cell properties in cancer stem cells in the brain." "In fact," she said, "normal stem cells and cancer stem cells share properties and functions." She added that targeting Id proteins in cancer stem cells might, "lead to more effective therapies for malignant brain tumours".

What does this mean for me?

Better understanding of how neural (and other) stem cells differentiate may influence when and where injected stem cell therapies are used. Also, as Dr Lasorella said (above), studying processes involved in stem cell regulation may give insight into similar processes in cancerous stem cells leading to malignant brain tumours.

What does this mean for science?

This study presents a new idea - it was previously thought that the niche itself controls the release of NSCs with chemical signals. Here we see the decision is influenced, at least in part, by the NSC's internal wiring. More generally, the central role of Id proteins is another good example of multi-tasking, involving co-ordination between internal wiring of differentiation and the cell's external environment.

Reference:

Niola, F., Zhao, X., Singh, D., Castano, A., Sullivan, R., Lauria, M., Nam, H., Zhuang, Y., Benezra, R., Di Bernardo, D., Iavarone, A., & Lasorella, A. (2012). Id proteins synchronize stemness and anchorage to the niche of neural stem cells Nature Cell Biology, 14 (5), 477-487 DOI: 10.1038/ncb2490