Adult Stem Cells Reprogammed In Their Natural Environment
Article Date: 01 Jul 2008 - 3:00 PDT
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'
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
http://www.medicaln
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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