Mature B Cells Reprogrammed To Stem-cell-like State
ScienceDaily (Apr. 21, 2008) — Fully mature, differentiated B cells
can be reprogrammed to an embryonic-stem-
use of an egg according to a study published in Cell.
In previous research, induced pluripotent stem (IPS) cells have been
created from fibroblasts, a specific type of skin cells that may
differentiate into other types of skin cells. Because there is no way
to tell if the fibroblasts were fully differentiated, the cells used
in earlier experiments may have been less differentiated and
therefore easier to convert to the embryonic-stem-
IPS cells.
B cells are immune cells that can bind to specific antigens, such as
proteins from bacteria, viruses or microorganisms. Unlike
fibroblasts, mature B cells have a specific part of their DNA cut out
as a final maturation step. "Once that piece of DNA is cut out, it
can't come back," says Jacob Hanna, first author on the paper and a
postdoctoral fellow in Whitehead Member Rudolf Jaenisch's
lab. "Checking the genome give us a way to make sure the resulting
IPS cells were not from immature cells."
Hanna and his colleagues began the experiment by generating IPS cells
from immature B cells. Similar to the process used to create IPS
cells from fibroblast cells, Hanna successfully reprogrammed the
immature B cells into IPS cells by using retroviruses to transfer
four genes (Oct4, Sox2, c-Myc and Klf4) into the cells' DNA.
However, an additional factor, CCAAT/enhancer-
(C/EBP±), was needed to nudge mature B cells to be reprogrammed as
IPS cells.
Like IPS cells from earlier fibroblast studies, the IPS cells from
both the mature and immature B cells could be used to create mice.
The mice grown from the reprogrammed mature B cells were missing the
same part of their DNA as the mature B cells, demonstrating that
Hanna and his colleagues had successfully reprogrammed fully
differentiated cells.
In addition to demonstrating the power of reprogramming, this work
offers the promise of powerful new mouse models for autoimmune
diseases such as multiple sclerosis and type 1 diabetes, in which the
body attacks certain types of its own cells. For example, mature B or
T cells specific for nerve cells called glia could be reprogrammed to
IPS cells and then used to create mice with an entire immune system
that is primed to only attack the glia cells, thereby creating a
mouse model for studying multiple sclerosis.
Eventually, researchers will be able to study diseases by following a
similar process with human cells, predicts Jaenisch, who is also a
professor of biology at Massachusetts Institute of Technology. "In
principle, this will allow you to transfer a complex genetic human
disease into a Petri dish, and study it," he says. "That could be the
first step to analyze the disease and to define a therapy."
This research was supported by the National Institutes of Health and
the Helen Hay Whitney Foundation.
Journal reference: Direct reprogramming of terminally differentiated
mature B lymphocytes to pluripotency. Cell, April 18, 2008 134(2)
Authors and affiliations: Jacob Hanna (1), Styliani Markoulaki (1),
Patrick Schorderet (1), Caroline Beard (1), Bryce W. Carey (1),
Marius Wernig (1), Menno P. Creyghton (1), Eveline J. Steine (1),
(1), John P. Cassady (1), Christopher J. Lengner (1), Jessica A.
Dausman (1), Rudolf Jaenisch (1,2)
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 USA
Department of Biology, MIT, Cambridge, MA 02142 USA
Adapted from materials provided by Whitehead Institute for Biomedical
Research, via EurekAlert!, a service of AAAS.
Need to cite this story in your essay, paper, or report? Use one of
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MLA Whitehead Institute for Biomedical Research (2008, April 21).
Mature B Cells Reprogrammed To Stem-cell-like State. ScienceDaily.
Retrieved April 22, 2008, from http://www.scienced
/releases/2008/
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StemCells subscribers may also be interested in these sites:
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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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