When Is a Stem Cell Not a Stem Cell?
By Nick Zagorski
Johns Hopkins Medicine
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 Aug. 26 in Nature, could simplify the
isolation of stem cells from not only 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," said author Nicholas Gaiano, assistant
professor at the university's 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glowing, indicating that the CBF1 protein was no longer active in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," Gaiano said. "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 Institute of Neurological
Disorders and Stroke, a member of NIH; Burroughs Wellcome Fund; and
Sidney Kimmel Foundation for Cancer Research.
Authors on the paper are Kenichi Mizutani, Keejung Yoon, Louis Dang,
Akinori Tokunaga and Gaiano, all of Johns Hopkins.
http://www.jhu.
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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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