[GRG] NewAbs: Mechanism behind Blood Stem Cells’ Longevity at U. Penn

Clive: FYI. — Steve Coles
At 01:06 PM 11/26/2013, GRG wrote:

http://www.upenn.edu/pennnews/news/researchers-penn-uncover-

Mechanism-behind-Blood-Stem-Cells-Longevity “Researchers at Penn Uncover
Mechanism Behind Blood Stem Cells’ Longevity”
Media Contact:
Evan Lerner elerner@upenn.edu
215-573-6604
 
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
produced
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
asymmetrically, so
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
the School
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 Université 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
cells responsible
for making these cells can last for decades without being
exhausted.”
    The standing theory to explain these cells’ near
immortality is asymmetric division, though the cellular mechanism that
enables
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
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.
    The researchers believe these findings could
eventually lead to the ability to regrow blood stem cells after
chemotherapy treatments
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
Association.

L. Stephen Coles, M.D., Ph.D., Co-Founder
Los Angeles Gerontology Research GroupURL:
http://www.grg.org
E-mail: scoles@grg.orgE-mail:
scoles@ucla.edu

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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