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Researchers at Penn uncover mechanism behind blood stem cells' longevity
Date:11/26/2013

for this phenomenon, the researchers analyzed all of the genes expressed in the stem cells and their more rapidly dividing progeny. Proteins that only went to one side of the dividing cell, the researchers thought, might play a role in partitioning other key factors responsible for keeping one side a stem cell.

They saw different expression patterns of the motor protein myosin II, which has two forms, A and B. Myosin II is the protein that enables the body's muscles to contract, but in nonmuscle cells it is also used in cell division, where it helps cleave and close off the cell walls as the cell splits apart.

"We found that the stem cell has both types of myosin," Shin said, "whereas the final red and white blood cells only had the A form. We inferred that the B form was key to splitting the stem cells in an asymmetric way that kept the B form only in the stem cell."

With these myosins as their top candidate, the researchers labeled key proteins in dividing stem cells with different colors and put them under the microscope.

"We could see that the myosin IIB goes to one side of the dividing cell, which causes it to cleave differently," Discher said. "It's like a tug of war, and the side with the B pulls harder and stays a stem cell."

The researchers then performed in vivo tests using mice that had human stem cells injected into their bone marrow. By genetically inhibiting myosin IIB production, the researchers saw the stem cells and their early progeny proliferating while the amount of downstream blood cells dropped.

"Because the stem cells were not able to divide asymmetrically, they just kept making more of themselves in the marrow at the expense of the differentiated cells," Discher said.

The researchers also used a drug that temporarily blocked both A and B forms of myosin II, finding that it increased the prevalence of non-dividing stem cells, blocking the more rapid division of progeny.'/>"/>

Contact: Evan Lerner
elerner@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert  

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