New Technique Produces Genetically Identical Stem Cells
Main Category: Stem Cell Research
Also Included In: Genetics; Biology / Biochemistry
Article Date: 02 Jul 2008 - 5:00 PDT
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Adult cells of mice created from genetically reprogrammed cells - so-
called induced pluripotent stem (IPS) stem cells - can be triggered
via drug to enter an embryonic-stem-
for further genetic alteration.
The discovery, which promises to bring new efficiencies to embryonic
stem cell research, is reported in the July 1, 2008, online issue of
Nature Biotechnology.
"This technical advancement will allow thousands of identical
reprogrammed cells to be used in experiments,
one of the paper's two lead authors and a postdoctoral researcher in
Whitehead Member Rudolf Jaenisch's lab.
"Using these cells could help define the milestones of how cells are
reprogrammed and screen for drug-like molecules that replace the
potentially cancer-causing viruses used for reprogramming,
Christopher Lengner, the other lead author and also a postdoctoral
researcher in the Jaenisch's lab.
In the current work, Wernig and Lengner made mice created in part
from the embryonic-stem-
cells were created by reprogramming adult skin cells using
lentiviruses to randomly insert four genes (Oct4, Sox2, c-Myc and
Klf4) into the cells' DNA. The IPS cells also were modified to switch
on these four genes when a drug trigger, doxycycline, is added to the
cells.
Wernig and Lengner then took cells from each IPS mouse and introduced
the doxycycline trigger, thereby changing the adult mouse cells into
IPS cells.
While earlier reprogramming experiments have typically induced
pluripotency in adult skin cells, Wernig and Lengner were able to
employ this novel method to successfully reprogram multiple cell and
tissue types, including cells of the intestine, brain, muscle,
kidney, adrenal gland, and bone marrow. Importantly, the technique
allows researchers to create large numbers of genetically identical
IPS cells, because all cells in the mouse contain the same number of
viral integrations in the same location within the genome. With
previous approaches, each reprogrammed cell differed because the
viruses used to insert the reprogramming genes could integrate
anywhere in the cell's DNA with varying frequency.
Wernig and Lengner's method also increases the reprogramming
efficiency from one in a thousand cells to one in twenty.
The large numbers of IPS cells that can be created by this method can
aid experiments requiring millions of identical cells for
reprogramming, such as large-scale chemical library screening assays.
"In experiments, the technique will eliminate many of the
reprogramming process's unpredictable variables and simplify
enormously the research on the reprogramming mechanism and the
screening for virus replacements,
professor of biology at Massachusetts Institute of Technology.
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Article adapted by Medical News Today from original press release.
------------
The research was supported by the Human Frontiers Science
Organization Program, the Ellison Medical Foundation, the Ruth L.
Kirschstein National Research Service Award, and the National
Institutes of Health.
Written by Nicole Giese
Rudolf Jaenisch's primary affiliation is with Whitehead Institute for
Biomedical Research, where his laboratory is located and all his
research is conducted. He is also a professor of biology at
Massachusetts Institute of Technology.
Full citation:
Nature Biotechnology (online), July 1, 2008
A novel drug-inducible transgenic system for direct reprogramming of
multiple somatic cell types
Marius Wernig (1), Christopher J Lengner (1), Jacob Hanna (1),
Michael Lodato (1,2), Eveline Steine (1), Ruth Foreman (1,2), Judith
Staerk (1), Styliani Markoulaki (1), and Rudolf Jaenisch (1,2).
1. Whitehead Institute for Biomedical Research, 9 Cambridge Center,
Cambridge, MA 02142, USA
2. Department of Biology, Massachusetts Institute of Technology, 31
Ames Street, Cambridge, Massachusetts 02139, USA
Source: Cristin Carr
Whitehead Institute for Biomedical Research
http://www.medicaln
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Cord Blood Registry
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