Posted on 09/12/2005 2:15:26 PM PDT by sourcery
What exactly makes a stem cell a stem cell? The question may seem simplistic, but while we know a great deal of what stem cells can do, we don't yet understand the molecular processes that afford them such unique attributes.
Now, researchers at Whitehead Institute for Biomedical Research working with human embryonic stem cells have uncovered the process responsible for the single-most tantalizing characteristic of these cells: their ability to become just about any type of cell in the body, a trait known as pluripotency.
"This is precisely what makes these stem cells so interesting from a therapeutic perspective," says Whitehead Member Richard Young, senior author on the paper which will be published September 8 in the early online edition of the journal Cell. "They are wired so they can become almost any part of the body. We've uncovered a key part of the wiring diagram for these cells and can now see how this is accomplished."
Once an embryo is a few days old, the stem cells start to differentiate into particular tissue types, and pluripotency is forever lost. But if stem cells are extracted, researches can keep them in this pluripotent state indefinitely, preserving them as a kind of cellular blank slate. The therapeutic goal then is to take these blank slates and coax them into, say, liver or brain tissue. But in order to guide them out of pluripotency with efficiency, we need to know what keeps them there to begin with.
Researchers in the Whitehead laboratories of Young, Rudolf Jaenisch, MIT-computer scientist David Gifford, and the Harvard lab of Douglas Melton focused on three proteins known to be essential for stem cells. These proteins, Oct4, Sox2, and Nanog, are called "transcription factors," proteins whose job is to regulate gene expression. (Transcription factors are really the genome's primary movers, overseeing, coordinating, and controlling all gene activity.)
These proteins were known to play essential roles in maintaining stem cell identity--if they are disabled, the stem cell immediately begins to differentiate and is thus no longer a stem cell. "But we did not know how these proteins instructed stem cells to be pluripotent," says Laurie Boyer, first author on the paper and a postdoctoral scientist who divides her time between the Jaenisch and Young labs.
Using a microarray technology invented in the Young lab, Boyer and her colleagues analyzed the entire genome of a human embryonic stem cell and identified the genes regulated by these three transcription factors. The research team discovered that while these transcription factors activate certain genes essential for cell growth, they also repress a key set of genes needed for an embryo to develop.
This key set of repressed genes produce additional transcription factors that are responsible for activating entire networks of genes necessary for generating many different specialized cells and tissues. Thus, Oct4, Sox2, and Nanog are master regulators, silencing genes that are waiting to create the next generation of cells. When Oct4, Sox2, and Nanog are inactivated as the embryo begins to develop, these networks then come to life, and the stem cell ceases to be a stem cell.
The new work provides the first wiring diagram of human embryonic stem-cell regulatory circuitry. "This gives us a framework to further understand how human development is regulated," says Boyer.
"These findings provide the foundation for learning how to modify the circuitry of embryonic stem cells to repair damaged or diseased cells or to make cells for regenerative medicine," says Young. "They also establish the foundation for solving circuitry for all human cells." ###
This research was funded by the National Human Genome Research Institute and the National Institutes of Health. Richard Young consults for Agilent Technologies, manufacturers of his microarray platform.
This Venn diagram represents how stem-cell master regulators Oct4, Nanog, and Sox2 work together in regulating the genome. It shows the number of genes that they interact with individually, in pairs, or as a triad. (Image courtesy of Whitehead Institute for Biomedical Research)
Ping
Excellently designed mechanism.
"This" is completely irrelevant to the crevo debate one way or the other.
How'd I do?
very exciting news ping.
Hmm foundational research.
So far, the cry to have the government fund ESC research is as if there was a cry to create delicious sandwiches using only subatomic particles: Far more complicated than it has to be, especially with usable intermediates reaping results.
This can be overcome through the use of powerful drugs that disable your immune system, but they leave you vulnerable to all sorts of diseases the rest of your life.
Embryonic stem cells necessarily come from "somebody else" even if you don't think they are a "somebody"!
Where they have been used, the recipients developed cancer.
The best bet appears to be the development of a technology that extracts your OWN stem cells (of whatever type), grows them in vast numbers, and then reinjects them. This way your immune system is tricked into not eating them!
BTW, the initial idea behind using embryonic stem cells was they had apparantly not developed to the extent that they would be incompatible with someone else's cells. Of course, that was garbage. They are identified.
Do I understand this correctly?
... we need to experiment with pluripotent cells
in order to understand them enough
in order to to make them into cells
that aren't pluripotent.
Agreed. Stem-cell research isn't exactly right for the evolution ping list, and I really wish someone would start up a list devoted to this kind of article. Still, considering how much anti-science posting we get in the evolution threads, this is worth cranking up the ping machine ...
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To be clear though, I have nothing against and in fact am all for research using CBE's harvested from cord blood. To that I am willing to contribute tax money, to creating embryos to harvest stem cells I am willing to contribute nothing.
I know what the atheists will say, "This was completely an accident involving amino acids in a puddle that got caught in the lightning storm one day and were zapped. The rest is history, and the human wrist and human foot are the marvels of biological engineering they are today."
In other words,
"What a happy accident."
Obviously a noodly appendage is at work.
And with that, cry havoc and let slip the dogs of war. Right.
I wouldn't mind maintaining such a list, but how would it be described? The wave-of-the-future ping? I mean, what exactly are the parameters you'd have in mind?
Agreed--thanks for ping.
For what it's worth: the source for stem-cells in research is one (contentious) issue, but the science of understanding the structure and behaviour of stem cells should n't push anyone's buttons, it is wonderous and beautiful. I keep a healthy handful of salt at the ready when it comes to some of the claims for potential therapies that might be enabled--jury's out, but let's let them deliberate
How about you ask the director of one of the institutes which funded this research his opinion?
Francis S. Collins has been the director of the National Institutes of Health's National Human Genome Research Institute (NHGRI) since 1993. Before that, he was a research geneticist at the University of Michigan, where he and his colleagues were the first to clone the gene for cystic fibrosis. A practicing Christian, Collins is particularly interested in the ethical implications of human genetics research.
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