Clive: FYI. — Steve Coles
At 01:06 PM 11/26/2013, GRG wrote:
Mechanism-behind-Blood-Stem-Cells-Longevity “Researchers at Penn Uncover
Mechanism Behind Blood Stem Cells’ Longevity”
Evan Lerner firstname.lastname@example.org
November 25, 2013; The blood stem cells that live in bone marrow are at
the top of a complex family tree. Such stem cells split and
divide down various pathways that ultimately produce red cells, white
cells, and platelets. These “daughter” cells must be
at a rate of about one million per second to constantly replenish the
body’s blood supply.
Researchers have long wondered what allows these stem
cells to persist for decades, when their progeny last for days, weeks or
months before they need to be replaced. Now, a study from the University
of Pennsylvania has uncovered one of the mechanisms that
allow these stem cells to keep dividing in perpetuity.
The researchers found that a form of the motor
protein that allows muscles to contract helps these cells divide
that one part remains a stem cell while the other becomes a daughter
cell. Their findings could provide new insight into blood
cancers, such as leukemia, and eventually lead to ways of growing
transfusable blood cells in a lab.
The research was conducted by Dennis Discher,
Professor in the Department of Chemical and Biomolecular Engineering in
of Engineering and Applied Science, and members of his lab: lead author
Jae-Won Shin, Amnon Buxboim, Kyle R. Spinler, Joe Swift,
Dave P. Dingal, Irena L. Ivanovska, and Florian Rehfeldt. They
collaborated with researchers at the UniversiteÃ de Strasbourg,
Lawrence Berkeley National Laboratory and University of California in San
Francisco. It was published in the journal Cell Stem Cell.
“Your blood cells are constantly getting worn out and
replaced,” Discher said. “We want to understand how the stem
for making these cells can last for decades without being
The standing theory to explain these cells’ near
immortality is asymmetric division, though the cellular mechanism that
this kind of division was unknown. Looking to identify the forces
responsible 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
The researchers then performed in vivo tests using
mice that had human stem cells injected into their bone marrow. By
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
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
of non-dividing stem cells, blocking the more rapid division of
The researchers believe these findings could
eventually lead to the ability to regrow blood stem cells after
for blood cancers or even for growing blood products in the lab.
Finding a drug that can temporarily shut down only the B form of
myosin, while leaving the A form alone, would allow the stem cells to
divide symmetrically and make more of themselves without
preventing their progeny from dividing themselves.
“Nonetheless, the currently available drug that
blocks both the A and B forms of myosin II could be useful in the
clinic,” Shin said,
“because donor bone marrow cultures can now easily be enriched for
blood stem cells, and those are the cells of interest in transplants.
Understanding the forces that stem cells use to divide can thus be
exploited to better control these important cells.”
The research was supported by the National Institutes
of Health, Human Frontier Science Program, and American Heart
L. Stephen Coles, M.D., Ph.D., Co-Founder
Los Angeles Gerontology Research GroupURL: