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A protein that
controls the formation of different types of mature blood cells could play an important
role in developing new treatments for blood diseases and helping realize the
potential of regenerative medicine.
A study led by researchers
from Cincinnati Children’s, published online Oct. 7 in the Journal of
Experimental Medicine, sheds new light on the function of RhoA, a GTPase protein
that serves as a molecular switch in guiding blood cell formation.
RhoA is necessary
for regulating the final stage of cell division in progenitor cells as they produce
several kinds of adult blood cells. Mutations in the RhoA pathway have been
linked to certain immune disorders including human combined immunodeficiency, which
makes people highly susceptible to infections.
Finding ways to
control this pathway could lead to improved treatments for this and other blood
diseases, immune disorders and cancers. The new study also could be useful for researching
approaches to regenerative medicine, in which pluripotent stem cells could be
used to repair or regrow damaged tissues.
“We show that
RhoA deficiency causes hematopoietic failure in all lines of blood cells and
results in defective hematopoietic progenitor cells,” said Yi Zheng, PhD, lead investigator and director of Experimental Hematology and Cancer Biology at Cincinnati Children’s. “This is also
important to understanding diseases like pancytopenia, in which people don’t
produce enough mature red and white blood cells and platelets. In regenerative
medicine, it appears RhoA function would need to be artfully controlled to
obtain functional blood cells.”
Zheng and colleagues
conducted a series of experiments in mouse models to confirm their data. In one
test, the team transplanted stem cells from mice bred to lack RhoA into another
group of mice. The RhoA-deficient stem
cells achieved long term engraftment, but they were unable to produce new
progenitor cells or differentiated blood cells. In another test, the
researchers were able to reconstitute RhoA in the cells, which restored the
normal function of hematopoietic stem and progenitor cells.
Now Zheng’s team
is testing prospective small-molecule inhibitors developed at Cincinnati
Children’s that could treat disease by blocking abnormal RhoA pathway functions.
Article written by Nick Miller, Cincinnati
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