There is a certain protein that plays a major role in embryonicstem cells. Oct4
controls the genes that stop stem cells from becoming specialised into any of the
200 or so types of cell in the human body - blood, bone, muscle, hair etc.
Researchers have long believed that Oct4 is also important in stopping adult stem cells from becoming specialised. Indeed more than 50 studies have reported finding
that Oct4 is active in adult stem cells.
But those findings are misleading, according to research in the lab of Rudolf Jaenisch
at the Whitehead Institute for Biomedical Research. The research is published online
in Cell Stem Cells on October 10.
Postdoctoral fellow Christopher Lengner has shown that Oct4 is not needed to maintain
adult stem cells in their undifferentiated state in mice. He has also shown that
adult tissues work normally when no Oct4 is present.
Lengner used three independent methods to try to detect Oct4 in several tissue types
in which other researchers had reported finding it. Either no trace of Oct4, or so
little as to be indistinguishable from background readings, was found in all of these.
This is an important finding. It means that pluripotency is regulated differently
in adult and embryonicstem cells.Pluripotency is the ability of stem cells to change
into any kind of cell.
“This is the definitivesurvey of Oct4,” says Jaenisch, who is also an MIT professor
of biology. “It puts all those claims of pluripotent adult stem cells into perspective.”
Oct4 maintains the pluripotency of embryonicstem cells. But only for a short time
before the embryo implants in the wall of the uterus. After this Oct4 is turned off
and the cells differentiate into over 200 cell types in the body.
“We have convincingly shown that Oct4 has no role in adult stem cells,” says Lengner.
The aim of the research was to find out how well tissues that had been shown to express
Oct4 worked without the protein. These tissues included brain, bone marrow, hair
follicle and the lining of the intestine.
To study this, Lengner bred mice in which the Oct4 gene had been deleted from a given
tissue type. Next he stressed the tissue in several ways. This forced the adult stem cells within to regenerate the tissue. All of them regenerated normally.
Lengner and his colleagues then tested to make sure that Oct4 had indeed been deleted
from the cells.
Finally they set out to validate the published reports that claimed Oct4 was expressed
in these types of adult stem cell. Using highly sensitive methods that could detect
Oct4 at the single cell level, they were unable to confirm the earlier reports.
“This is a cautionary tale of believing what you read in the literature,” says Lengner.
He suggests that earlier studies might have misapplied tricky techniques. Or they
could have worked with cell cultures that had spent too much time in an incubator.
“We now know that adult stem cellsregulate their pluripotency, or ‘stemness’, using
different mechanisms from embryonicstem cells, he says. He and his colleagues are
now studying these mechanisms.
Is there one pathway that controls stemness in different adult stem cells, Lengner
wonders - or does each type of stem cell have its own pathway?
"We don’t yet know.”
“Oct4 is dispensable for somatic stem cell self-renewal”
Christopher J. Lengner(1), Fernando D. Camargo(1), Konrad Hochedlinger(3), G. Grant
Welstead(1), Samir Zaidi(2), Sumita Gokhale(1), Hans R. Scholer(4), Alexey Tomilin(5)
and Rudolf Jaenisch(1)(2)
There is a protein that stops embryonic stem cells from becoming specialised. What
is it called?
Many studies seem to have shown that this same protein stops what from becoming specialised?
This new study seems to show that those studies were wrong because of two things
that Christopher Lengner has shown. One was that Oct4 is not needed to stop adult
stem cells from specialising. What was the other?
Oct4 stops embryonic stem cells from turning into other cells. Another way to say
this is that Oct4 maintains the ------------of embryonic stem cells.
Lengner bred mice in which no Oct4 was produced in certain tissues. If Oct4 was actually
needed to stop adult stem cells from specialising what would have happened to the
adult stem cells in those tissues?
How did the scientists know that that hadn't happened?
This told them that Oct4 wasn't needed for what?
How do the Cambridge scientists explain all the other results that seemed to show
So we now have 50 studies showing one thing and one study showing exactly the opposite.
What do you think will happen next?
Who do you think is right and why?
Learning and teaching resources
The Genetics Science Learning Center at Utah University is an excellent source of
classroom resources and activities for teachers - as well as providing animations
and illustrations such as those we've linked to in the story above. Simple registration
allows access to the teacher materials.
There is for example a nice webquest on stem cell at http://web.mit.edu/biology/www/
while an activity that probes students' positions on stem cell research and calls
for them to explain their reasoning can be found at http://learn.genetics.utah.edu/units/stemcells/print-and-go/scthink.cfm
Click herefor the full list of teacher resources at the Genetics Science Learning
Teachers’ Domain also has a wealth of classroom resources and activities on stem
cells. Again simple registration is required.