In recent years, stem cell researchers have become very adept at manipulating
the fate of adult stem cells cultured in the lab. Now, researchers at the Salk
Institute for Biological Studies achieved the same feat with adult neural stem
cells still in place in the brain. They successfully coaxed mouse brain stem
cells bound to join the neuronal network to differentiate into support cells
instead.
The discovery, which is published ahead of print on
Nature
Neuroscience's website, not only attests to the versatility of neural stem
cells but also opens up new directions for the treatment of neurological
diseases, such as multiple sclerosis, stroke and epilepsy that not only affect
neuronal cells but also disrupt the functioning of glial support cells.
"We have known that the birth and death of adult stem cells in the brain
could be influenced be experience, but we were surprised that a single gene
could change the fate of stem cells in the brain," says the study's lead author,
Fred H. Gage, Ph.D., a professor in the Laboratory for Genetics and the Vi and
John Adler Chair for Research on Age-Related Neurodegenerative Diseases.
Throughout life, adult neural stem cells generate new brain cells in two
small areas of mammalian brains: the olfactory bulb, which processes odors, and
the dentate gyrus, the central part of the hippocampus, which is involved in the
formation of memories and learning.
After these stem cells divide, their
progenitors have to choose between several options - remaining a stem cell,
turning into a nerve cell, also called a neuron, or becoming part of the brain's
support network, which includes astrocytes and oligodendrocytes.
Astrocytes are star-shaped glia cells that hold neurons in place,
nourish them, and digest parts of dead neurons. Oligodendrocytes are specialized
cells that wrap tightly around axons, the long, hair-like extensions of nerve
cell that carry messages from one neuron to the next. They form a fatty
insulation layer, known as myelin, whose job it is to speed up electrical
signals traveling along axons.
When pampered and cosseted in a petri
dish, adult neural stem cells can be nudged to differentiate into any kind of
brain cell but within their natural environment in the brain career options of
neural stem cells are thought to be mostly limited to neurons.
"When we
grow stem cells in the lab, we add lots of growth factors resulting in
artificial conditions, which might not tell us a lot about the in vivo
situation," explains first author Sebastian Jessberger, M.D., formerly a
post-doctoral researcher in Gage's lab and now an assistant professor at the
Institute of Cell Biology at the Swiss Federal Institute of Technology in
Zurich. "As a result we don't know much about the actual plasticity of neural
stem cells within their adult brain niche."
To test whether stem cells
in their adult brain environment can still veer off the beaten path and change
their fate, Jessberger used retroviruses to genetically manipulate neural stem
cells and their progeny in the dentate gyrus of laboratory mice. Under normal
conditions, the majority of newborn cells differentiated into neurons. When he
introduced the Ascl1, which had previously been shown to be involved in the
generation of oligodendrocytes and inhibitory neurons, he successfully
redirected the fate of newborn cells from a neuronal to an oligodendrocytic
lineage.
"It was quite surprising that stem cells in the adult brain
maintain their fate plasticity and that a single gene was enough to reprogram
these cells," says Jessberger. "We can now potentially tailor the fate of stem
cells to treat certain conditions such as multiple sclerosis."
In
patients with multiple sclerosis, the immune system attacks oligodendrocytes,
which leads to the thinning of the myelin layer affecting the neurons' ability
to efficiently conduct electrical signals. Being able to direct neural stem
cells to differentiate into oligodendrocytes may alleviate the symptoms.
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Article adapted by Medical News Today
from original press release.----------------------------
Researchers who also contributed to the study include postdoctoral
researchers Nicolas Toni, Ph.D., Gregory D. Clemenson Jr, Ph.D., and Jasodhara
Ray, Ph.D., all in the Laboratory of Genetics.
The Salk Institute for
Biological Studies in La Jolla, California, is an independent nonprofit
organization dedicated to fundamental discoveries in the life sciences, the
improvement of human health and the training of future generations of
researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the
crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a
gift of land from the City of San Diego and the financial support of the March
of Dimes.
Source: Gina Kirchweger
Salk Institute
