|Scientists Identify a Mouse Embryonic Stem Cell
More Like Our Own
Scientists have discovered a new type of mouse embryonic stem
cell that is the closest counterpart yet to human embryonic stem
(ES) cells, the National Institutes of Health (NIH) announced today.
The cells are expected to serve as an improved model for human
ES cells in studies of regeneration, disease pathology and basic
stem cell biology.
The findings, reported on-line June 27 in Nature, are
the result of a collaborative effort among scientists at the National
Institute of Neurological Disorders and Stroke (NINDS), the National
Cancer Institute (NCI) — both part of NIH — and the
University of Oxford, U.K.
Mouse ES cells are typically used as a proxy for human ES cells,
even though they differ in several ways, from their appearance
under a microscope to chemical modifications in their DNA. The
stem cells isolated by Dr. Ron McKay, Ph.D., the study's lead scientist
and a senior investigator at NINDS, are a closer match to human
ES cells by these measures and others. Moreover, because they’re
farther along the developmental timeline than the traditionally
studied cells, they could offer scientists a unique glimpse at
a critical point in the life of an ES cell — a time when
it is poised to start producing mature cell types, including neurons,
muscle and bone.
One key to isolating the new stem cells was to work with slightly
older mouse embryos. Traditionally studied mouse ES cells come
from embryos that haven't yet implanted themselves in the uterine
wall. The new cells come from the epiblast, a cluster of cells
that forms after implantation. In mammals, the epiblast will give
rise to all the cells that make up the adult animal, while surrounding
tissues will become supportive structures like the placenta.
Another key was to grow the mouse epiblast cells using methods
developed for growing human ES cells, an innovation made by Paul
Tesar, a graduate student in the NIH-Oxford Biomedical Research
Scholars program. The program has allowed Mr. Tesar to split his
time between the two institutions; it also provided a link between
Dr. McKay and Professor Sir Richard Gardner, an expert on mouse
embryonic development at Oxford.
To characterize the epiblast stem cells, the researchers first
tested whether they are capable of becoming diverse cell types — a
defining feature of ES cells. The epiblast stem cells passed two
such tests. When grown in test tubes, the cells also morphed — or
differentiated — into neuron-like cells, muscle cells, and
cells found in the body's inner organs, depending on the growth
medium. When injected into immunodeficient mice, they formed teratomas — large
tumors containing bits of cartilage, muscle, fat, skin and other
Other experiments revealed how similar the epiblast stem cells
are to human ES cells, and how different those two cell types are
from the classic mouse ES cell. For instance, human ES cells and
mouse epiblast stem cells possess nearly the same set of active
transcription factors — proteins that turn genes on and off.
They also have similar chemical tags on their DNA, making it more
or less receptive to transcription factors.
"Understanding what stem cells are and how they grow in a dish
are still central problems in medical research," said Dr. McKay. "If
we know how to control their growth and differentiation, we can
regenerate cells lost to injury or disease."
With such knowledge, for example, adult human cells could be reprogrammed
to act more like human ES cells. One lab recently coaxed mouse
skin cells to behave like classic mouse ES cells; the new mouse
epiblast cell could be the key to extending this same trick to
Dr. McKay emphasized that despite their importance, the new cells
won't render the classic mouse ES cells obsolete. The classic cells
are easier to grow and are the primary tool that researchers use
to create mouse models of human genetic diseases.
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