[GRG] First production of different cells using transcription factors on stem cells

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Contact: Igor Slukvin
islukvin@wisc.edu
608-263-0058
University of Wisconsin-Madison

Wisconsin scientists find genetic recipe to turn stem cells to
blood

IMAGE: Two transcription factors are all that is required to make
blood from pluripotent stem cells. Following introduction of the
factors, stem cells form endothelium (green) which subsequenty
become blood cells…

MADISON, Wis. — The ability to reliably and safely make in the
laboratory all of the different types of cells in human blood is
one key step closer to reality.

Writing today in the journal Nature Communications, a group led by
University of Wisconsin-Madison stem cell researcher Igor Slukvin
reports the discovery of two genetic programs responsible for
taking blank-slate stem cells and turning them into both red and
the array of white cells that make up human blood.

The research is important because it identifies how nature itself
makes blood products at the earliest stages of development. The
discovery gives scientists the tools to make the cells themselves,
investigate how blood cells develop and produce clinically relevant
blood products.

“This is the first demonstration of the production of different
kinds of cells from human pluripotent stem cells using
transcription factors,” explains Slukvin, referencing the proteins
that bind to DNA and control the flow of genetic information, which
ultimately determines the developmental fate of undifferentiated
stem cells.

During development, blood cells emerge in the aorta, a major blood
vessel in the embryo. There, blood cells, including hematopoietic
stem cells, are generated by budding from a unique population of
what scientists call hemogenic endothelial cells. The new report
identifies two distinct groups of transcription factors that can
directly convert human stem cells into the hemogenic endothelial
cells, which subsequently develop into various types of blood cells.

The factors identified by Slukvin’s group were capable of making
the range of human blood cells, including white blood cells, red
blood cells and megakaryocytes, commonly used blood products.

“By overexpressing just two transcription factors, we can, in the
laboratory dish, reproduce the sequence of events we see in the
embryo” where blood is made, says Slukvin of the Department of
Pathology and Laboratory Medicine in the UW School of Medicine and
Public Health and the Wisconsin National Primate Research Center.

The method developed by Slukvin’s group was shown to produce blood
cells in abundance. For every million stem cells, the researchers
were able to produce 30 million blood cells.

A critical aspect of the work is the use of modified messenger RNA
to direct stem cells toward particular developmental fates. The new
approach makes it possible to induce cells without introducing any
genetic artifacts. By co-opting nature’s method of making cells and
avoiding all potential genetic artifacts, cells for therapy can be
made safer.

“You can do it without a virus, and genome integrity is not
affected,” Slukvin notes. Moreover, while the new work shows that
blood can be made by manipulating genetic mechanisms, the approach
is likely to be true as well for making other types of cells with
therapeutic potential, including cells of the pancreas and heart.

An unfulfilled aspiration, says Slukvin, is to make hematopoietic
stem cells, multipotent stem cells found in bone marrow.
Hematopoietic stem cells are used to treat some cancers, including
leukemia and multiple myeloma. Devising a method for producing them
in the lab remains a significant challenge.

“We still don’t know how to do that,” Slukvin notes, “but our new
approach to making blood cells will give us an opportunity to model
their development in a dish and identify novel hematopoietic stem
cell factors.”

The study was conducted under the umbrella of the Progenitor Cell
Biology Consortium, run by National Heart, Lung and Blood
Institute, part of the National Institutes of Health, and involved
a collaboration of scientists at UW-Madison, the Morgridge
Institute for Research, the University of Minnesota at the Twin
Cities and the Houston Methodist Research Institute.

In addition to Slukvin, authors of the new report include Irina
Elcheva, Vera Brok-Volchanskaya, Akhilesh Kumar, Patricia Liu,
Jeong-Hee Lee, Lilian Tong and Maxim Vodyanik, all of the Wisconsin
National Primate Research Center; Scott Swanson, Ron Stewart and
James A. Thomson of the Morgridge Institute for Research; Michael
Kyba of the University of Minnesota’s Lillehei Heart Institute; and
Eduard Yakubov and John Cooke of the Center for Cardiovascular
Regeneration of the Houston Methodist Research Institute.

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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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