<p>Single factor converts adult stem cells into embryonic-like stem cells</p>
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
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.eurekalert.org/pub_releases/2007-11/cp-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
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…" the
researchers concluded. "Future studies will 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."