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the CBF1 protein was no longer active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.
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