Contact: Igor Slukvin
University of Wisconsin-Madison
Wisconsin scientists find genetic recipe to turn stem cells to
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
“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
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
“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
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.