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Master switches found for adult blood stem cells
February 12, 2007Johns Hopkins Kimmel Cancer Center scientists have found a set of "master switches" that keep adult blood-forming stem cells in their primitive state. Unlocking the switches' code may one day enable scientists to grow new blood cells for transplant into patients with cancer and other bone marrow disorders.
The scientists located the control switches not at the gene level, but farther down the protein production line in more recently discovered forms of ribonucleic acid, or RNA. MicroRNA molecules, once thought to be cellular junk, are now known to switch off activity of the larger RNA strands which allow assembly of the proteins that let cells grow and function.
"Stem cells are poised to make proteins essential for maturing into blood cells, but microRNAs keep them locked in their place," says cancer researcher Curt Civin, M.D., Ph.D., who led the study. The journal account will appear online the week of February 5 in the early edition of the Proceedings of the National Academy of Sciences.
To halt protein assembly, microRNAs pair up with matching full-length RNA, then fold and twist it, rendering the larger RNA useless. But the RNA pairings are not perfect, and one microRNA can latch on to several hundred RNA strands. "They act like a single circuit breaker to efficiently control hundreds of RNAs," says Civin, the Herman and Walter Samuelson Professor of Cancer Research.
"We're looking for ways to flip these microRNA switches, to control when stem cells grow into new blood cells," says Robert Georgantas, Ph.D., research associate at the Johns Hopkins Kimmel Cancer Center and first and corresponding author of the study.
To identify the key microRNAs, Georgantas sifted through thousands of RNA pieces with a custom-built, computer software program. Its algorithms let the software, fed data from samples of blood and bone marrow from healthy donors, match RNA pairs. The outcome was a core set of 33 microRNAs that match with more than 1,200 of the larger variety RNA already known to be important for stem-cell maturation.
Georgantas and Civin currently are testing whether these pair predictions are valid by using a non-reproducing virus to insert genetic instructions for each of the 33 microRNAs into adult stem cells. They'll then be cultured in Petri dishes. MicroRNA-155 — the first microRNA tested — was predicted to stop stem cells from developing into red and white blood cells. As expected, stem cells without microRNA-155 matured: they formed approximately 75 red and 150 white blood cell colonies per dish. Stem cells with microRNA-155 matured into far fewer red and white cell colonies — about seven and 30 per dish, respectively.
"Using microRNAs to stall an adult blood stem cell in its early stage could help us grow new ones in test tubes, and perhaps give us more insight into stem-cell maturation for other tissue types," says Civin.
Johns Hopkins Medical Institutions
To halt protein assembly, microRNAs pair up with matching full-length RNA, then fold and twist it, rendering the larger RNA useless. But the RNA pairings are not perfect, and one microRNA can latch on to several hundred RNA strands. "They act like a single circuit breaker to efficiently control hundreds of RNAs," says Civin, the Herman and Walter Samuelson Professor of Cancer Research.
"We're looking for ways to flip these microRNA switches, to control when stem cells grow into new blood cells," says Robert Georgantas, Ph.D., research associate at the Johns Hopkins Kimmel Cancer Center and first and corresponding author of the study.
To identify the key microRNAs, Georgantas sifted through thousands of RNA pieces with a custom-built, computer software program. Its algorithms let the software, fed data from samples of blood and bone marrow from healthy donors, match RNA pairs. The outcome was a core set of 33 microRNAs that match with more than 1,200 of the larger variety RNA already known to be important for stem-cell maturation.
Georgantas and Civin currently are testing whether these pair predictions are valid by using a non-reproducing virus to insert genetic instructions for each of the 33 microRNAs into adult stem cells. They'll then be cultured in Petri dishes. MicroRNA-155 — the first microRNA tested — was predicted to stop stem cells from developing into red and white blood cells. As expected, stem cells without microRNA-155 matured: they formed approximately 75 red and 150 white blood cell colonies per dish. Stem cells with microRNA-155 matured into far fewer red and white cell colonies — about seven and 30 per dish, respectively.
"Using microRNAs to stall an adult blood stem cell in its early stage could help us grow new ones in test tubes, and perhaps give us more insight into stem-cell maturation for other tissue types," says Civin.
Johns Hopkins Medical Institutions
Stem Cells Current Events and Stem Cells News RSSFirst use of antibody and stem cell transplantation to successfully treat advanced leukemia
For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
Magnetic nanoparticles to simultaneously diagnose, monitor and treat
Whether it's magnetic nanoparticles (mNPs) giving an army of 'therapeutically armed' white blood cells direction to invade a deadly tumour's territory, or the use of mNPs to target specific nerve channels and induce nerve-led behaviour (such as the life-dependant thumping of our hearts), mNPs have come a long way in the past decade.
Of mice and men: Stem cells and ethical uncertainties
The recent creation of live mice from induced pluripotent stem cells (iPSCs) not only represents a remarkable scientific achievement, but also raises important issues, according to bioethicists at The Johns Hopkins University's Berman Institute of Bioethics.
NIH-funded researchers transform embryonic stem cells into human germ cells
Researchers funded in part by the National Institutes of Health have discovered how to transform human embryonic stem cells into germ cells, the embryonic cells that ultimately give rise to sperm and eggs.
Stem cell therapy may offer hope for acute lung injury
Researchers at the University of Illinois at Chicago College of Medicine have shown that adult stem cells from bone marrow can prevent acute lung injury in a mouse model of the disease.
Placental precursor stem cells require testosterone-free environment to survive
Trophoblast stem cells (TSCs), cells found in the layer of peripheral embryonic stem cells from which the placenta is formed, are thought to exhibit "immune privilege" that aids cell survivability and is potentially beneficial for cell and gene therapies.
Endocrine Society calls for expanded scope and funding for stem cell research
Stem cell research holds great promise for the treatment of millions of Americans with debilitating and possibly fatal diseases.
Experimental treatments restore partial vision to blind people
Two experimental treatments, a retinal prosthesis and fetal tissue transplant, restored some vision to people with blinding eye diseases. The findings, presented at Neuroscience 2009, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news on brain science and health, may lead to new treatments for the blind.
Scientists demonstrate link between genetic defect and brain changes in schizophrenia
Researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion - a mutation that confers the highest known genetic risk for schizophrenia - is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.
Small mechanical forces have big impact on embryonic stem cells
Applying a small mechanical force to embryonic stem cells could be a new way of coaxing them into a specific direction of differentiation, researchers at the University of Illinois report. Applications for force-directed cell differentiation include therapeutic cloning and regenerative medicine.
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