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Cancer-Causing Gene Crucial in Stem Cell Development, Study Finds
http://www.sciencedaily.com/releases/2010/09/100902121047.htm
ScienceDaily (Sep. 3, 2010) — Stem cells might be thought of as trunks
in the tree of life. All multi-cellular organisms have them, and they
can turn into a dazzling variety other cells -- kidney, brain, heart
or skin, for example. One class, pluripotent stem cells, has the
capacity to turn into virtually any cell type in the body, making them
a focal point in the development of cell therapies, the conquering of
age-old diseases or even regrowing defective body parts.
Now, a research team at the University of Georgia has shown for the
first time that a gene called Myc (pronounced "mick") may be far more
important in the development and persistence of stem cells than was
known before. Myc is traditionally thought of as a cancer-causing
gene, or oncogene, but recent studies from the UGA team have
established critical roles for it in stem cell biology. The discovery
has important implications for the basic understanding of
developmental processes and how stem cells can be used for therapeutic
purposes.
"This new research has uncovered a really unexpected role for Myc,"
said Stephen Dalton, GRA Eminent Scholar of Molecular Cell Biology and
Georgia Cancer Coalition Distinguished Scientist at UGA. "Our work
here represents the first mechanistic characterization of how Myc
controls the pluripotent stem cell state."
The research was published in the journal Cell Stem Cell. Other
authors of the paper include Keriayn Smith and Amar Singh of the
Dalton lab at UGA. Smith left recently to begin a postdoc at the
University of North Carolina. Dalton also is a member of the
department of biochemistry and molecular biology in the Franklin
College of Arts and Sciences and is affiliated with the UGA Cancer
Center and the Biomedical and Health Sciences Institute.
In previous work, Dalton and his colleagues showed that Myc is
critical for stem cell maintenance and that it affects widespread
changes in gene expression. This latter function is crucial when stem
cells differentiate into more specific cell types. In the new
research, Dalton's team showed that Myc sustains the important
pluripotency process by repressing a "master regulator" gene called
GATA6.
"Pluripotency is the inherent property of a cell to create all cell
types, from an embryo to an adult organism," said Dalton. "It's an
extremely important biological process, and knowing how it is
controlled is crucial not only from a basic developmental perspective
but also so that we can harness the potential of stem cells for the
development of therapies, including those for diabetes, cardiovascular
disease and a range of neurological disorders. Through a detailed
understanding of early development, we hope to apply this information
so that pluripotent stem cells can be differentiated into
therapeutically useful cell types. These cells can then be used in a
clinical setting to cure degenerative diseases and treat acute
injury."
The finding that Myc inhibits GATA6 came as a big surprise to the
Dalton team and points out that researchers have only seen the tip of
the "molecular iceberg" in terms of what Myc does in stem cells. It
now seems likely that understanding Myc's role in further detail will
reshape current ideas about the basic biology of stem cells.
Dalton's new work addressed the uncertainty about how Myc maintains
the pluripotency of stem cells by examining what happens when two
forms of Myc -- c-Myc and N-Myc -- are inactivated in pluripotent stem
cells. What he found was that either c- or N-Myc is sufficient to
maintain pluripotency, but that the absence of both triggers the
differentiation of pluripotent stem cells. Myc is therefore acting as
a "brake" to restrain differentiation. When the "differentiation
brake" is removed, cells lose their stem cell properties, and,
potentially, they can become any one of over a hundred different cell
types.
Pluripotent stem cells can now be made from skin fibroblasts and even
from blood samples. (Fibroblasts are cells common in connective
tissues of animals and play an important role in the healing of
wounds, among many functions.) The conversion of mature fibroblast or
blood cells back to pluripotent stem cells is called "reprogramming."
Myc also has a critical role in this process. The ability to make stem
cells from a patient's blood or skin is going to revolutionize
medicine as it opens the way for patient-specific stem cells that
would circumvent problems associated with immune rejection, said
Dalton.
"During the reprogramming of cells, Myc represses genes associated
with the differentiated state and primes them for the expression of
stem cell genes," he said. "We now speculate that during the early
reprogramming stage, Myc serves to change the cell cycle so that stem
cells can divide for long periods of time without aging. This is also
what Myc does in cancer cells."
Dalton said that there is an intriguing relationship between normal
stem cells and cancer cells. Since Myc is crucial for maintenance of
stem cells and for the development of cancer, pluripotent stem cells
represent a good model for tumor biologists. Cancer is thought to be
initiated by rogue stem cells found in different tissues, further
highlighting the link between stem cell biology, cancer and Myc.
"This is clearly going to be a major area of research for many years
to come," Dalton said.
The research was supported by grants to Dalton from the National
Institute of Child Health and Development and the National Institute
for General Medical Sciences.
Story Source:
The above story is reprinted (with editorial adaptations by
ScienceDaily staff) from materials provided by University of Georgia,
via EurekAlert!, a service of AAAS.
Journal Reference:
1. Keriayn N. Smith, Amar M. Singh, Stephen Dalton. Myc Represses
Primitive Endoderm Differentiation in Pluripotent Stem Cells. Cell
Stem Cell, 2010; 7 (3): 343-354 DOI: 10.1016/j.stem.2010.06.023
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"Ethics" is simply a last-gasp attempt by deist conservatives and
orthodox dogmatics to keep humanity in ignorance and obscurantism,
through the well tried fermentation of fear, the fear of science and
new technologies.
There is nothing glorious about what our ancestors call history,
it is simply a succession of mistakes, intolerances and violations.
On the contrary, let us embrace Science and the new technologies
unfettered, for it is these which will liberate mankind from the
myth of god, and free us from our age old fears, from disease,
death and the sweat of labour.
Rael
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