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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 reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Bone Implant Offers Hope for Skull Deformities
A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?
Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure.
Paradoxical protein might prevent cancer
One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
The use of stem cells in regenerative medicine may also be detrimental for health
The use of stem cells in regenerative medicine is not always beneficial for human health, it may even be harmful according to a work done by the University of Granada and University of León. Scientists have demonstrated that transplantation of human mononuclear cells isolated from umbilical cord blood exerted a deleterious effect in rats with liver cirrhosis.
Penn Study Provides First Clear Idea of How Rare Bone Disease Progresses
An international team of scientists, led by researchers at the University of Pennsylvania School of Medicine, is taking the first step in developing a treatment for a rare genetic disorder called fibrodysplasia ossificans progressiva (FOP), in which the body's skeletal muscles and soft connective tissue turns to bone, immobilizing patients over a lifetime with a second skeleton.
Iowa State University researcher discovers key to vital DNA, protein interaction
A researcher at Iowa State University has discovered how a group of proteins from plant pathogenic bacteria interact with DNA in the plant cell, opening up the possibility for what the scientist calls a "cascade of advances."
Scientists successfully reprogram blood cells
Researchers have transplanted genetically modified hematopoietic stem cells into mice so that their developing red blood cells produce a critical lysosomal enzyme -preventing or reducing organ and central nervous system damage from the often-fatal genetic disorder Hurler's syndrome.
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