Under different conditions, neural stem cells can differentiate into a plethora of different cells. The work described in the previous section about isolation relies on one side of the coin; that neural stem cells do indeed differentiate into different cell types. By definition, that functionality is what characterized neural stem cells. The other side of that coin is the influence of extracellular factors on differentiation. This is basically the crux of the "Nature vs. Nurture" debate. Regardless of where we draw the line between nature and nurture, the answer will always be a little from column A, a little from column B. I'd say that the deterministic "nature" aspect lies in the nucleus of the cell and all the DNA encoded in it. The nurture side would be all the chemical influences, etc. that affect the development of the cell. I don't know about you, but this is pretty convincing to me that nature and nurture are completely intertwined, and should not bee seen as two polar opposites.
So, philosophical debates... eh, fugetaboutit! How does it work? What does it have to do with stem cells? Well, to really get into how it all works is beyond the scope of this website, but basically a big focus on genetics is central to this section. I won't bore you with the hairy details, I'll just keep it specific to stem cells.
Once scientists have identified and isolated their stem cells, it would be nice if these precious cells could survive outside of the body. The ways that scientists achieve this is by supplying their stem cells with growth factors such as epidermal growth factor (EGF) or fibroblast growth factor (FGF-2). The differentiation of cells is usually promoted by fetal bovine serum (FBS).
After ensuring that their cells can live in vitro, the first concern of neuroscientists engaged in stem cell research is whether or not new cells are actually generated. The important protein for identifying newly differentiated cells is bromodeoxyuridine (BrdU). Click here for a protocol for the procedure of identifying new cells using BrdU.
After cells have differentiated, scientists want answers to questions like, "How many?" and "What kind?" This process is made possible by the same type of immunocytochemistry as described in the section on identifying stem cells. The methodology remains the same, but different antibodies specific to different protein markers are used. This is because differentiated cells are of a different phenotype than their stem cell progenitors.
How the different cell types of the central nervous system are generated during normal development is one of the central questions in the field of neurobiology. It is one of the most interesting topics, and we are now only scratching the surface of this fascinating field. The best I can report to you are small pieces of the big picture. Another hairy issue is the fact that a lot of research done on the factors and methods involved in the differentiation of neural stem cells is very recent and very valuable. Many scientists have chosen to patent their techniques, and are not available to the general public without monetary compensation.
In the past, biologists have identified many, many different substances that have been categorized as growth factors of some sort. A complete listing of these factors and cytokines can be found at www.copewithcytokines.de .
Very recently, a team of Italian scientists have explored the tendency of neural stem cells to differentiate into non-neural cells, such as blood cells. This greatly broadens the spectrum of possibilities and demands more research into the precursors of all cells in the body. Their data supports the idea that the surfaces of neural stem cells express a number of non-neural receptors. This leads us to believe that the successful transplantation of neural stem cells to replace damaged systems is not only due to the cells themselves, but their responsivity to external signals. It has also been shown that adult neurogenesis is accompanied by changes in vascular structures which may be explained by the potential of stem cells to differentiate into blood cells.
Vescovi, Galli, and Gritti are three scientists who have done some really impressive work in the transdifferentiation capacity of neural stem cells. When experimenting with neural stem cells in vitro, they found that the ration of neuronal to glial cells was significantly altered by the addition or removal of various extracellular signals. The very same signals used in vitro have now been injected in vivo into the lateral ventricles. The findings show that it elicits proliferation of resident stem cells and the generation of neurons and glia that migrate all over the brain.
One finding, that is agreed upon by many scientists, is that the core genetic program involving basic helix-loop-helix(bHLH) transcription factors is necessary for the differentiation of stem cells into neurons. The family of bHLH transcription factors are commonly referred to as the proneural proteins.
Moreover, non-neural stem cells, like the ones found in bone marrow, are not as plastic as those found in the brain. Go-go gray matter! The next section deals with some of the different factors that scientists have made use of in growing cultures of neurons.