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When is a stem cell not really a stem cell?
August 27, 2007Working with embryonic mouse brains, a team of Johns Hopkins scientists seems to have discovered an almost-too-easy way to distinguish between "true" neural stem cells and similar, but less potent versions. Their finding, reported this week in Nature, could simplify the isolation of stem cells not only from brain but also other body tissues.
What the researchers identified is a specific protein "signal" that appears to prevent neural stem cells - the sort that might be used to rebuild a damaged nervous system - from taking their first step toward becoming neurons. "Stem cells don't instantly convert into functional adult tissue," says author Nicholas Gaiano, Ph.D., assistant professor at the Institute for Cell Engineering. "They undergo a stepwise maturation where they gradually shed their stem cell properties."
The first step turns stem cells into "progenitor" cells by dictating how signals downstream of a protein called Notch, which regulates stem cells in many different tissues, are transmitted. One well known target of Notch is a protein called CBF1. To help study Notch signaling further, Gaiano and his team created genetically engineered mouse embryos that glow green when CBF1 is turned on.
To their surprise, they noticed that during brain development some of the brain cells generally thought to be neural stem cells stopped glowing, indicating that the CBF1 protein was no longer active in them. A closer look revealed that those cells that went dark were in fact no longer true neural stem cells, which can form all major brain cell types, but instead had aged into progenitor cells, which form mostly neurons.
They tested whether CBF1 was the critical switch by chemically knocking out the protein in neural stem cells. The knockout got the stem cells to rapidly convert to progenitor cells. "However, if we activated the CBF1 protein in progenitor cells we couldn't get them to shift back into stem cells," says Gaiano. "So whatever happens biochemically once CBF1 is turned off seems to create a one-way street."
Another recent study, using the mouse line generated by the Gaiano group, found that CBF1 signaling may play the same role in blood stem cells, leading Gaiano to suspect that his team's discovery might be a general "switch" distinguishing stem cells from progenitors in many different tissues.
Johns Hopkins Medical Institutions
To their surprise, they noticed that during brain development some of the brain cells generally thought to be neural stem cells stopped glowing, indicating that the CBF1 protein was no longer active in them. A closer look revealed that those cells that went dark were in fact no longer true neural stem cells, which can form all major brain cell types, but instead had aged into progenitor cells, which form mostly neurons.
They tested whether CBF1 was the critical switch by chemically knocking out the protein in neural stem cells. The knockout got the stem cells to rapidly convert to progenitor cells. "However, if we activated the CBF1 protein in progenitor cells we couldn't get them to shift back into stem cells," says Gaiano. "So whatever happens biochemically once CBF1 is turned off seems to create a one-way street."
Another recent study, using the mouse line generated by the Gaiano group, found that CBF1 signaling may play the same role in blood stem cells, leading Gaiano to suspect that his team's discovery might be a general "switch" distinguishing stem cells from progenitors in many different tissues.
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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