When is a stem cell not really a stem cell?
Working with embryonic mouse brains, a team of Johns Hopkins
scientists seems to have discovered an almost-too-easy way to
distinguish between "true" neural stem cells and similar, but less
potent versions. Their finding, reported this week in Nature, could
simplify the isolation of stem cells not only from brain but also
other body tissues.
What the researchers identified is a specific protein "signal" that
appears to prevent neural stem cells the sort that might be used to
rebuild a damaged nervous system from taking their first step
toward becoming neurons. "Stem cells don't instantly convert into
functional adult tissue," says author Nicholas Gaiano, Ph.D.,
assistant professor at the Institute for Cell Engineering. "They
undergo a stepwise maturation where they gradually shed their stem
cell properties."
The first step turns stem cells into "progenitor" cells by dictating
how signals downstream of a protein called Notch, which regulates
stem cells in many different tissues, are transmitted. One well known
target of Notch is a protein called CBF1. To help study Notch
signaling further, Gaiano and his team created genetically engineered
mouse embryos that glow green when CBF1 is turned on.
To their surprise, they noticed that during brain development some of
the brain cells generally thought to be neural stem cells stopped
glowing, indicating that the CBF1 protein was no longer active in
them. A closer look revealed that those cells that went dark were in
fact no longer true neural stem cells, which can form all major brain
cell types, but instead had aged into progenitor cells, which form
mostly neurons.
They tested whether CBF1 was the critical switch by chemically
knocking out the protein in neural stem cells. The knockout got the
stem cells to rapidly convert to progenitor cells. "However, if we
activated the CBF1 protein in progenitor cells we couldn't get them
to shift back into stem cells," says Gaiano. "So whatever happens
biochemically once CBF1 is turned off seems to create a one-way
street."
Another recent study, using the mouse line generated by the Gaiano
group, found that CBF1 signaling may play the same role in blood stem
cells, leading Gaiano to suspect that his team's discovery might be a
general "switch" distinguishing stem cells from progenitors in many
different tissues.
###
The research was funded by the National Institutes of Health (NINDS),
the Burroughs Wellcome Fund, and the Sidney Kimmel Foundation for
Cancer Research.
Authors on the paper are Ken-ichi Mizutani, Keejung Yoon, Louis Dang,
Akinori Tokunaga and Gaiano, all of Johns Hopkins.
On the Web:
http://www.hopkins-
www.nature.com
Public release date: 26-Aug-2007
Contact: Nick Zagorski
nzagors1@jhmi.
443-287-2251
Johns Hopkins Medical Institutions
http://www.eurekale
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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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