(Press-News.org) Athens, Ga. – 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 today 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.
END
Kidney transplants that show a combination of fibrosis (scarring) and inflammation after one year are at higher risk of long-term transplant failure, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN).
To identify these abnormalities, doctors would need to perform routine biopsies on apparently normal kidney transplants—rather than waiting for problems to occur. "Even for some transplants that would be expected to have a very long graft survival, protocol biopsies performed in the first year may indicate the ...
Researchers at the University of California, San Diego School of Medicine have identified the molecular mechanism that makes omega-3 fatty acids so effective in reducing chronic inflammation and insulin resistance.
The discovery could lead to development of a simple dietary remedy for many of the more than 23 million Americans suffering from diabetes and other conditions.
Writing in the advance online edition of the September 3 issue of the journal Cell, Jerrold Olefsky, MD, and colleagues identified a key receptor on macrophages abundantly found in obese body fat. ...
DURHAM, N.C. – Duke University Medical Center researchers have found two genes in mice which might help identify why some people are more susceptible than others to potentially deadly staph infections.
The researchers uncovered important genetic clues that ultimately could help inform patient management and drug development.
"If you know up front that a patient is at risk for developing an Staphylococcus aureus infection, then you will be better able to manage them clinically, give them preventive measures, and treat them more aggressively if they become ill," said ...
Results of a study reported in the September issue of the Journal of the American Geriatrics Society suggest that Veterans with post-traumatic stress disorder (PTSD) have a greater risk for dementia than Veterans without PTSD, even those who suffered traumatic injuries during combat.
Exposure to life threatening events, like war, can cause PTSD, and there are high rates among veterans. PSTD includes symptoms such as avoiding things or people that remind a person of the trauma, nightmares, difficulty with sleep, and mood problems.
"We found Veterans with PTSD had ...
DURHAM, N.H. – New research from the University of New Hampshire shows that the "gateway effect" of marijuana – that teenagers who use marijuana are more likely to move on to harder illicit drugs as young adults – is overblown.
Whether teenagers who smoked pot will use other illicit drugs as young adults has more to do with life factors such as employment status and stress, according to the new research. In fact, the strongest predictor of whether someone will use other illicit drugs is their race/ethnicity, not whether they ever used marijuana.
Conducted by UNH associate ...
Roberto Carlos' free kick goal against France in 1997's Tournoi de France is thought by many to have been the most skilful free kick goal - from 35m with a powerful curling banana trajectory - ever scored; but by others to have been an incredible fluke.
Taken in 1997, a year before the French won the World Cup, Brazilian Carlos's goal held France to a frustrating draw but, now, a group of French physicists – perhaps with a nostalgic eye to a happier time for French football – have computed the trajectory and shown that Carlos' goal was no fluke.
The research published ...
Heidelberg, 3 September 2010 – Our cerebral cortex, or pallium, is a big part of what makes us human: art, literature and science would not exist had this most fascinating part of our brain not emerged in some less intelligent ancestor in prehistoric times. But when did this occur and what were these ancestors? Unexpectedly, scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have now discovered a true counterpart of the cerebral cortex in an invertebrate, a marine worm. Their findings are published today in Cell, and give an idea of what ...
Montreal, September 3, 2010 – Dr. Éric A. Cohen, Director of the Human Retrovirology research unit at the Institut de recherches cliniques de Montréal (IRCM), and his team published yesterday, in the online open-access journal PLos Pathogens, the results of their most recent research on the role of the Vpr protein in HIV (human immunodeficiency virus) infection and AIDS (acquired autoimmune deficiency syndrome).
"We previously identified that HIV, when infecting target cells, blocks cell division and induces cell death," says Dr. Cohen. "We then discovered that the Vpr ...
A new discovery by scientists at the Universities of East Anglia and Frankfurt could make it possible in future to identify the source of banned CFCs that are probably still being released into the atmosphere.
Using mass spectrometers, the researchers analysed air samples collected in the stratosphere by balloons belonging to the French space agency, the Centre National d'Etudes Spatiales (CNES). They discovered the largest chlorine isotope enrichment ever found in nature.
CFCs were banned in most countries because of their depletion of the ozone layer. Due to their ...
New York, NY, September 2, 2010—16.6 million small business employees work in firms that will be eligible for tax credits under the Affordable Care Act (ACA), according to a new Commonwealth Fund report. The credits, designed to offset health insurance premium costs and help small businesses afford and maintain health insurance, are available in taxable years beginning in 2010. Researchers estimate that by 2013, 3.4 million workers may work in firms that take advantage of the tax credit. The tax credits increase in value in 2014, from up to 35 percent of the employer's ...
