such as "Introduction", "Conclusion"..etc
March 20, 2003 — CAMBRIDGE, MA – Only 1
percent to 3 percent of animals cloned from adult cells survive to
birth; many die mysteriously very early in development, around the time
of implantation. A new study suggests that a set of genes important in
early development fails to reactivate in adult, or somatic,
cell-derived clones, a finding that could help scientists skirt a major
roadblock in cloning.
"Most animals cloned from somatic cells fail in all seven species,
while animals cloned from embryonic stem cells survive much better,"
said Rudolf Jaenisch, a researcher at Whitehead Institute for
Biomedical Research and co-author of the new study, published in the
current online issue of the journal Development. "We wanted to know why
embryonic stem-cell derived clones survive so well while those derived
from somatic cells do so poorly."
Scientists already knew that among those genes essential to normal
embryonic development is the Oct4 gene, which prompts embryos to create
pluripotent cells – cells that can form any tissue in the body.
Researchers working with Whitehead Institute member David Page
identified more than 60 genes that are expressed in normal mouse
embryos. With an eye toward the Oct4 gene, they whittled the larger set
of genes down to 10 that behave similarly to Oct4.
A team of scientists at Whitehead Institute and the University of
Hawaii cloned two types of mouse embryos: one derived from embryonic
stem cells and another from somatic cells. Scrutiny of the clones'
genetic activity revealed that those made from embryonic stem cells
expressed all 10 genes normally, while only 62 percent of somatic
cell-derived clones correctly expressed the genes, said Alex Bortvin, a
postdoctoral associate at Whitehead Institute and lead author of this
"This finding suggests that other genes that function together with
Oct4 in control of early development also might be inefficiently
expressed in somatic clones," Bortvin said.
Because the genes are involved in early development, they are turned
off in adult cells. But as the debate over embryonic stem cell research
continues, scientists must look to adult stem cells for cloning studies
that could yield vital information about disease and cell development.
So, figuring out how to help somatic cell-derived embryos survive to
birth is high on the minds of researchers such as Jaenisch and his
The scientists also are curious about the role Oct4-related genes
play in pluripotency development, not an aim of this latest study.
"The functional importance of these genes has yet to be fully
investigated," said Bortvin, whose future research will involve a
deeper analysis of the function of Oct4-related genes.
At first glance, it may appear that the clones' failure to turn on
this set of genes is the key to understanding early clone development
failure. But the researchers are careful to note that while it may be
possible to figure out a way to reactivate Oct4-related genes in clones
created from somatic cells, that likely won't solve the problem of
"There are hundreds of genes that are not correctly expressed in
cloned animals," said Jaenisch, whose interest lies in therapeutic
cloning designed to study disease. "The issue now is to make cloning
This study, which is available now online, will be published in the
mid-April print edition of the journal Development. Study co-authors
include Kevin Eggan with Whitehead Institute; Helen Skaletsky and
Deborah Berry, both with the Howard Hughes Medical Institute and
Whitehead Institute; and Hidenori Akutsu and Ryuzo Yanagimachi, both
with the University of Hawaii. The research was supported by the Howard
Hughes Medical Institute and the National Institutes of Health.
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