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Was Hwang’s Stem Cells Parthenogenetic?
Friday,
03 August 2007
Researchers say they have confirmed suspicions that embryonic stem cells claimed
to be extracted from the first cloned human embryo by discredited South
Korean scientist Woo Suk Hwang actually owe their existence to
parthenogenesis, a process in which egg cells give rise to embryos without
being fertilized by sperm.
A committee formed by Seoul National University (SNU) concluded last year
that the 2004 cell line in question was not derived from SCNT. DNA
fingerprinting suggested the line was formed via parthenogenesis, but SNU
investigators later admitted to Korean media that the technique couldn't
determine for sure how the line was derived.
Genetic analysis has now confirmed that disgraced biologist Woo Suk Hwang
did not clone a human embryonic stem (ES) cell.
But the South Korean scientist's team inadvertently broke new ground by
creating the first human stem-cell line to come from an unfertilized egg,
say researchers. Other scientists have since replicated the feat, called
parthenogenesis.
"It's an unfortunate irony that
they didn't know what they had," said George Daley, a biologist at
Children's Hospital Boston who led the latest analysis.
"It would have been a very
important discovery," Daley said.
Discredited Korean embryonic stem
cells' true origins revealed
DNA analysis
finds they were the world's first human embryonic stem cells derived from
eggs alone
Public
release date: 2-Aug-2007
A report from researchers at Children's Hospital Boston and the Harvard
Stem Cell Institute sheds new light on a now-discredited Korean embryonic
stem cell line, setting the historical record straight and also
establishing a much-needed set of standards for characterizing human
embryonic stem cells. The report was published online August 2 by the
journal Cell Stem Cell.
In 2004, Korean investigators announced the creation of the world's first
human embryonic stem cells through somatic cell nuclear transfer, entailing
transfer of genetic material from a cell in the body into an egg. Now,
research led by Kitai Kim, PhD, and George Q. Daley, MD, PhD, of the
Children's Hospital Boston Stem Cell Program demonstrates that the Koreans
unwittingly created something entirely different – the world's first human
embryonic stem cell to be derived by parthenogenesis, a process that
creates an embryo containing genetic material only from the donor egg.
"We know now that the Koreans'
first supposed nuclear transfer-derived stem cell line was actually derived
from the woman's egg alone," Daley says.
The Koreans' 2004 paper, published in Science, was retracted by the journal
in early 2006 amid evidence that researchers Hwang Woo-Suk et al. had
falsified their data. An initial investigation of the Korean group's first
embryonic stem cell line suggested it might be parthenogenetic in origin,
but the analysis was inconclusive, and the cells' origin, until now, had
never been fully explained in a peer-reviewed journal.
Kim, Daley and collaborators used sophisticated genetic techniques to
compare mouse embryonic stem cells derived from different sources: from
embryos produced by natural fertilization; from embryos produced by
parthenogenesis (through artificial activation of unfertilized eggs); and
from embryos created through somatic cell nuclear transfer (replacing the
nucleus of an egg with the nucleus from a cell in the body). They also
tested three human embryonic stem cells isolated from fertilized embryos as
well as the Korean line of human cells claimed to have been created through
nuclear transfer.
They discovered that parthenogenetic embryonic stem cells have a distinct
genetic signature that reflects their biological origins. All cells
typically contain paired sets of chromosomes, one inherited from the mother
and the other from the father. During the process of parthenogenesis, one
set of chromosomes is duplicated, resulting in both chromosomes of the pair
being of one parental type or the other (a pattern called homozygosity,
which has reduced genetic diversity). Kim and Daley showed previously that
because chromosomes often exchange genetic material early in the process of
cell division that creates the egg (meiosis), the duplicated chromosomes
are not actually identical, but have places where the genes differ between
members of the pair (called heterozygosity). In embryonic stem cells of
parthenogenetic origin, this occurs especially toward the ends of the
chromosomes, which are more likely to exchange genetic material, rather
than the middle. In contrast, embryonic stem cells created through nuclear
transfer show a consistent pattern of variation through all regions of the
chromosome — thus making them easily distinguishable from parthenogenetic
cells.
The Korean cell line displays a genetic pattern that is clearly consistent
with a parthenogenetic origin, Kim and Daley now show.
Because mistakes during nuclear transfer can result in parthenogenetic
cells, Daley believes that the Hwang group generated parthenogenetic stem
cells by accident, and didn't have the tools to conclusively determine what
they had created. The first isolation of parthenogenetic stem cells from
humans would have been an important contribution, but the Hwang group's
attempt to pass off the cells as made by nuclear transfer was instead "a woeful case of misconduct,"
he says.
Parthenogenesis is a method of reproduction, common in plants and in some
animals, in which the female can generate offspring without the
contribution of a male. Daley's group has been stimulating parthenogenesis
in the laboratory as a way of creating customized embryonic stem cells that
can treat disease without being rejected by the immune system.
The team recently demonstrated in mice a feasible technique for generating
parthenogenetic embryonic stem cells that were genetically matched to the
egg donor at the genes that control tissue typing, and are attempting to
create similar cells from humans.
Daley, who is a member of the executive committee of the Harvard Stem Cell
Institute and president of the International Society for Stem Cell
Research, notes that scientists now have two powerful tools: human
parthenogenesis, which appears to be an efficient means of producing human
embryonic stem cells, and genetic screening, which can be used to scan stem
cells and help define their origins.
Daley imagines a future in which scientists could create a master bank of
parthenogenetic embryonic stem cells with genetically selected cells that
could be matched to patients on the genes that control immune rejection.
Having all the genetic materials come from the mother, as it does in
parthenogenesis, reduces tissue compatibility issues.
"There has been an advance in
the idea that you can couple parthenogenesis and genetic screening to
identify those cell lines that are going to be most helpful,"
Daley says.
Parthenogenetic embryonic stem cells do not obviate the need to also create
embryonic stem cells through nuclear transfer or from human embryos, he
adds.
"Each of the strategies has its
own applications, and there are certain types of research and certain
fundamental questions — and major areas of therapy — that can only be
accomplished with these other types of stem cells," Daley says.
Scientists prove that disputed Korean
stem cell line comes from an unfertilized egg and not cloning
Public
release date: 2-Aug-2007
Can a genetic signature identify the origin of a human stem cell line?
Scientists report that a widely available method for comprehensive genetic
analysis can help distinguish the type of human embryo that stem cells come
from. The research, to be published online August 2nd by the journal Cell
Stem Cell, published by Cell Press, also provides an intriguing new insight
into the largest scandal in the history of human stem cell research.
Different methods can be used to make embryonic stem (ES) cells. Human ES
cells are typically made from embryos that are donated by couples that have
undergone in vitro fertilization as a form of assisted reproduction therapy
for infertility. Parthenogenetic ES (pES) cells are derived from embryos
created by artificial activation of eggs in the absence of sperm. ES cells
generated by somatic nuclear transfer (ntES) are derived from embryos that
are created when the nucleus of an egg is replaced by the nucleus from a
body cell. Creation of human ntES and pES are of particular interest to
researchers as they may provide stem cells that are nearly genetically
identical to the donor and, therefore, particularly well suited for
customized, rejection-proof cell transplantation therapies.
To better understand the specific genetic recombination events that occur
in ES cells derived by these different methods, researchers under the
direction of Dr. George Q. Daley of Children’s Hospital Boston and the
Harvard Stem Cell Institute together with an international set of
collaborators completed a thorough genome-wide analysis of five novel pES
cells, 30 mouse ntES, as well as the SCNT-hES-1 cell line, the first human
ES cell line purportedly generated by Korean scientists using human eggs
and somatic cell nuclear transfer. The original paper describing the
SCNT-hES-1 cell line was retracted after an investigation by the Seoul
National University revealed research misconduct, but the derivation of the
cell line was never fully resolved.
The study found that ntES and pES cells have distinct DNA recombination
signatures. Those made from parthenogenetic embryos display a telltale
genetic pattern close to the centre of chromosomes. The results also
revealed that the SCNT-hES-1 cell line was not derived by somatic nuclear
transfer as was previously claimed.
“Our analysis shows that the
recombination pattern of SCNT-hES-1 is distinct from that of an ntES line
and is consistent with its derivation from a parthenogenetic embryo. Thus,
we conclude that the derivation of SCNT-hES-1 represented the first
successful isolation of human pES cells,” offers Dr. Daley.
The authors conclude that, although there are still significant obstacles
to overcome in the generation of pES cells, parthenogenesis is an efficient
way of generating embryos and that it may someday be feasible to generate
patient-specific pES cells from females.
“If careful genetic and functional
analysis of tissues derived from human pES cells show them to be safe and
effective, then pES cells might represent a favourable source for tissue
replacement therapies,” says Dr. Daley.
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