Drosophila neural stem cells in the central nervous system are labelled in green (membrane-targeted green fluorescent protein, GFP). Their large nucleoli (involved in cell growth) are shown in blue (stained for Fibrillarin). The nuclei of the surrounding neurons are labelled in red (stained for Elav).
Stem cells are often hailed for their medical potential, but the cells surrounding them can be just as important and may offer an alterative therapeutic strategy. Professor Andrea Brand and Dr James Chell of the Gurdon Institute, Cambridge, have uncovered the key role of glial cells in controlling stem cell division in the brain.
Stem cells are responsible for the maintenance and repair of diverse bodily tissues such as intestine, blood, and brain. A stem cell divides to generate a renewed stem cell, and a cell that will generate differentiated cell types, like neurons of the brain.
Stem cells spend much of their time in a dormant state, being activated when new cells are needed. Understanding how to activate stem cells may allow us to boost the regenerative capacity of the body in response to injury and degeneration.
Activity can be controlled by local signals within a tissue, or by systemic signals present in the circulation. These signals are often interpreted and relayed to the stem cells by their neighbours, which form a microenvironment known as the ‘stem cell niche’, key to the maintenance and control of stem cell populations.
In the larval stages of a developing fruitfly, neural stem cells in the brain are activated en masse in response to a nutritional stimulus, the protein in fly food. Our studies (PDF 3.3MB) found that this nutritional stimulus is relayed to neural stem cells by neighbouring glial cells (support cells abundant in the brain). These glial cells produce insulin-like molecules in response to nutrition that tell the dormant neural stem cells to grow and proliferate.
Interestingly, we know that a population of mammalian glial cells, known as astrocytes, also have the ability to produce insulin-like molecules. Previous studies have implicated the insulin-like growth factor, IGF-I, and the pathway it activates within cells, in the control of various stem cell populations. So it seems likely that human neural stem cells are regulated in the same way as fruitfly neural stem cells, with insulin-like molecules promoting the exit from dormancy and the production of new cells.
In our experiments we were able to genetically programme fruitfly glial cells to produce insulin-like molecules, irrespective of whether the nutritional stimulus was present. This meant we could activate neural stem cells when they would normally be dormant, a technique that could prove useful therapeutically in the future.
Stem cell research gives us a greater understanding of how organisms grow, remain stable, and repair themselves – an understanding that may one day allow us to replace cells when the body can’t do this for itself. Our research highlights the importance of IGF-I signalling in part of the process, as well as the potential of therapeutic strategies targeting the stem cells’ ‘neighbourhood’ rather than the stem cells themselves.
Andrea Brand
James Chell
Image credit: James Chell and Andrea Brand
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Filed under: Biomedical Sciences, Development, Ageing and Chronic Disease, Funding, Guest posts Tagged: Astrocytes, CNS, Developmental biology, Drosophila, Fruit fly, Glial cells, Gurdon Institute, James Chell, Professor Andrea Brand, Stem cells
