Single factor converts adult stem cells into embryonic-like stem cells
The simple recipe scientists earlier discovered for making adult stem
cells behave like embryonic-like stem cells just got even simpler. A
new report in the February 6th issue of the journal Cell, a Cell
Press publication, shows for the first time that neural stem cells
taken from adult mice can take on the characteristics of embryonic
stem cells with the addition of a single transcription factor.
Transcription factors are genes that control the activity of other
genes.
The discovery follows a 2006 report also in the journal Cell that
showed that the introduction of four ingredients could transform
differentiated cells taken from adult mice into "induced pluripotent
stem cells" (iPS) with the physical, growth, and genetic
characteristics typical of embryonic stem cells
(http://www.eurekale
Pluripotent refers to the ability to differentiate into most other
cell types. The same recipe was later shown to work with human skin
cells as well (http://www.eurekale
srt111307.php)
Subsequent studies found that the four-ingredient recipe could in
some cases be pared down to just two or three essential ingredients,
said Hans Schöler of the Max Planck Institute for Molecular
Biomedicine in Germany. "Now we've come down to just one that is
sufficient. In terms of the biology, it's really quite amazing."
The discovery sheds light on centuries-old questions about what
distinguishes the embryonic stem cells that give rise to egg and
sperm from other body cells, Schöler said. It might also have
implications for the use of reprogrammed stem cells for replacing
cells lost to disease or injury.
Other researchers led by Shinya Yamanaka showed that adult cells
could be reprogrammed by adding four factors – specifically Oct4,
Sox2, Klf4, and c-Myc. Recently, Schöler and his colleagues
demonstrated that Oct4 and Klf4 are sufficient to induce pluripotency
in neural stem cells.
By omitting Klf4 in the new study, they have now established that
Oct4 is the "driving force" behind the conversion of the neural stem
cells into iPS cells. The lone transcription factor is not only
essential, but it is also sufficient to make neural stem cells
pluripotent.
Those cells, which Schöler's team calls "1F iPS" can differentiate
into all three germ layers. Those primary germ layers in embryos
eventually give rise to all the body's tissues and organs. Not only
can those cells efficiently differentiate into neural stem cells,
heart muscle cells, and germ cells, they show, but they are also
capable of forming tumors when injected under the skin of nude mice.
Those tumors, or teratomas, contain tissue representing all three
germ layers. When injected into mouse embryos, the 1F iPS cells also
found their way into the animals' developing organs and were able to
be transmitted through the germ line to the next generation, they
report.
The results show that adult stem cells can be made pluripotent
without c-Myc and Klf4, both of which are "bona fide" oncogenes that
can help turn normal cells into cancer cells, Schöler said. Limiting
the number of factors is also a bonus because it means fewer genes
must be inserted into the genome, where they can potentially have
detrimental effects.
"Strikingly, Oct4 alone is sufficient to induce pluripotency in
neural stem cells, which demonstrates its crucial role in the process
of reprogramming…
show whether other sources of neural stem or progenitor cell
populations such as mouse or human bone marrow-derived mesenchymal
stem cells or dental pulp can be reprogrammed to iPS cells and
whether expression of Oct4 can be induced by non-retroviral means, a
prerequisite for the generation of iPS cells of therapeutic value."
###
The researchers include Jeong Beom Kim, Max Planck Institute for
Molecular Biomedicine, Munster, Germany; Vittorio Sebastiano, Max
Planck Institute for Molecular Biomedicine, Munster, Germany;
Guangming Wu, Max Planck Institute for Molecular Biomedicine,
Munster, Germany; Marcos J. Arauzo-Bravo, Max Planck Institute for
Molecular Biomedicine, Munster, Germany; Philipp Sasse, University of
Bonn, Bonn, Germany; Luca Gentile, Max Planck Institute for Molecular
Biomedicine, Munster, Germany; Kinarm Ko, Max Planck Institute for
Molecular Biomedicine, Munster, Germany; David Ruau, RWTH Aachen
University Medical School, Aachen, Germany; Mathias Ehrich, SEQUENOM
Inc., San Diego, CA; Dirk van den Boom, SEQUENOM Inc., San Diego, CA;
Johann Meyer, Hannover Medical School, Hannover, Germany; Karin
Hubner, Max Planck Institute for Molecular Biomedicine, Munster,
Germany; Christof Bernemann, Max Planck Institute for Molecular
Biomedicine, Munster, Germany; Claudia Ortmeier, Max Planck Institute
for Molecular Biomedicine, Munster, Germany; Martin Zenke, RWTH
Aachen University Medical School, Aachen, Germany; Bernd K.
Fleischmann, University of Bonn, Bonn, Germany; Holm Zaehres, Max
Planck Institute for Molecular Biomedicine, Munster, Germany; and
Hans R. Scholer, Max Planck Institute for Molecular Biomedicine,
Munster, Germany.
Public release date: 5-Feb-2009
[ Print Article | E-mail Article | Close Window ]
Contact: Cathleen Genova
cgenova@cell.
617-397-2802
Cell Press
http://www.eurekale
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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