The researchers examined a signaling pathway called TOR that the cells use to gauge nutrition levels and stress, said study senior author Dr. Julian A. Martinez-Agosto, an assistant professor of human genetics and pediatrics and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
“We wondered how an organism knows how many blood cells to make and when to make them in the context of injury and repair to tissue. In particular, we wondered how the blood progenitor cells sense that change and know when it’s time to make more blood cells,” Martinez-Agosto said. “We found that the TOR pathway uses these two genes to regulate its function and, when activated, it expands or increases the number of blood progenitor cells in the fly’s blood.”
The study appears Sept. 5, 2012 in the advance online issue of the peer-reviewed journal Development.
Michelle Dragojlovic-Munther, a graduate student in the Martinez-Agosto laboratory and first author of the study, found that cells with increased activity of TOR have a competitive advantage, allowing them to divide and make more of themselves so they can make blood. These progenitors, Dragojlovic-Munther found, also have high levels of reactive oxygen species (ROS) - ions or very small molecules that include free radicals – which are known to damage cells and can predispose humans to aging and heart disease. But in this case, the ROS proved valuable.
The precursors, Martinez-Agosto said, were producing ROS all the time and when TOR was activated, the levels increased dramatically. Too much ROS caused them to divide more than normal. If they treated the flies with antioxidants, which reduce ROS levels, the cells would develop normally.
The finding could be important because the TOR pathway is abnormally activated in many cancers, and it may be possible to target the levels of ROS, which may help regulate the pathway.
“What this study may be telling us is that too much ROS is causing more cells to divide and we may be able to target therapies that reduce ROS to significantly improve the condition,” Martinez-Agosto said, adding that specifically targeted antioxidants might be a potential treatment in certain subsets of blood disorders. “Sometimes that pathway is working more than it should, and we need the right amount of ROS for balance. It’s like Goldilocks, there can’t be too little or too much. We need it just right.”
Going forward, Martinez-Agosto and his team will try to determine where the ROS is coming from and perhaps discover an enzyme that may be a good target for therapeutics. They know that the higher ROS levels in blood progenitors are not coming from mitochondria, the cell’s power source, but have not identified how they are being produced.
“This study highlights mechanistic differences between TSC and PTEN on TOR function and demonstrates the multifaceted roles of a nutrient-sensing pathway in orchestrating proliferation and differentiation of myeloid-specific blood progenitors through regulation of ROS levels and the resulting myeloproliferative disorder when deregulated,” the study states.
The study was funded by a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health (GM007185) and the David Geffen School of Medicine at UCLA.
The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA’s Jonsson Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu.
Kim Irwin | Newswise Science News
Further reports about: > Broad Institute > Dragojlovic-Munther > Medicine > Precursor > Regenerative Therapien > Stem cell innovation > blood cell > blood flow > cell death > clinical application > embryonic stem cell > fly > fresh fruit > genes > human embryonic stem cell > methanol fuel cells > progenitor cells > suppressor
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy