How to convert connective tissue directly into neurons
January 14, 2013
Confocal micrograph of a primary human fibroblast cell grown in culture stained blue for actin, a highly abundant protein that makes up the cytoskeleton of cells. Energy-producing mitochondria are shown in green. (Credit: Matthew Daniels, University of Oxford and Wellcome Images)
Repression of a single protein in ordinary fibroblasts (connective tissue) is sufficient to directly convert them into functional neurons, scientists in the U.S. and China have discovered.
The findings could have far-reaching implications for the development of new treatments for neurodegenerative diseases like Huntington’s, Parkinson’s and Alzheimer’s.
In recent years, scientists have dramatically advanced the ability to induce pluripotent stem cells to become almost any type of cell, a major step in many diverse therapeutic efforts.
The new study focuses instead upon the surprising and singular role of PTB, an RNA-binding protein long known for its role in the regulation of alternative RNA splicing.
In in vitro experiments, scientists at University of California, San Diego School of Medicine and Wuhan University in China describe the protein’s notable regulatory role in a feedback loop that also involves microRNA — a class of small molecules that modulate the expression of up to 60 percent of genes in humans. Approximately 800 miRNAs have been identified and characterized to various degrees.
One of these miRNAs, known as miR-124, specifically modulates levels of PTB during brain development. The researchers found that when diverse cell types were depleted of PTB, they became neuronal-like cells or even functional neurons — an unexpected effect.
According to principal investigator Xiang-Dong Fu, PhD, professor of cellular and molecular medicine at UC San Diego, it’s not known which neuronal signal or signals trigger the loop. But the ability to artificially manipulate PTB levels in cells, inducing them to become neurons, offers tantalizing possibilities for scientists seeking new treatments for an array of neurodegenerative diseases.
It is estimated that over a lifetime, one in four Americans will suffer from a neurodegenerative disease, from Alzheimer’s and Parkinson’s to multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig’s disease). All of these diseases are currently incurable.
“If we learn how to manipulate PTB, which appears to be a kind of master regulator, we might eventually be able to avoid some of these problems by creating new neurons in patients using their own cells adjacent deteriorating neurons,” said Fu.
Funding for this research came, in part, from National Institutes of Health grants and the China 973 programs.
Comments (7)
by Press To Digitate
What would prevent these new techniques for converting fibroblasts (and others, demonstrated using skin tissue) into functioning neurons from being used to extend human cognition outside the brain, to a larger – potentially MUCH larger – fraction of our total anatomy? One might envision large increases in human intelligence through such dynamic modification of our epigenetic processes…
by Rashid Mostafa
If this line of discovery is successful, there will be so many improvements to health – both mental and physical – that we will be transformed. Ageing related diseases, depression, psychosis, cancer could all be reduced; who knows what could be achieved? Hooray for the National Institutes of Health grants and the China 973 programs! They sure know where to put their money.
by Ken
Life on Earth existed as a Soup-Sea for 3 billion years without the evolutionary impulse to complexity. How can this be? I suspect cells have a multitude of symbiotic options for dealing with geologic disasters.
by Bri
This is a fascinating discovery. Fairly recently there was an article about sponges having almost all the right structures to make working synapsis. Apparently their wasn’t any thinking functions related to these structures. Here we have a structure that we don’t associate with thinking and yet it is just a small modification away from being a nervous system component. This opens up a couple of areas of inquiry. First of all it seems that neurons are more primordial. Since turning off this protien reverts the cell to a neuron.. Obviously neurons have evolved to be very effective at processing information necessary for an organisms survival. In a which came first , the chicken or the egg kind of way, precursor neurons may have been present before organisms had diverse forms. Another possibility is that the structure of connective tissue is an extention of an organisms thinking and coordinating systems. We know that cells communicate chemically. Stem cells migrate to specific sites and then differentiate to exactly the right tissue. Maybe there is an underlining connection to these activities. A style of thinking that is slower and more suited for the microscopic world. As we start to understand how biological systems evolved, we may find that connective tissue is more brainy than it looks. It would make more sense in relation to the sponges synaptic precursers. Maybe they are thinking after all.
by Editor
Interesting ideas. They reminded me of something startling that neuroscientist Daniel Wolpert said in a TED Talk about “sea quints,” which digest their own brain and nervous system once they are attached to a rock and no longer need a brain, so I just posted it (see 01:45):
http://www.kurzweilai.net/daniel-wolpert-the-real-reason-for-brains. (It’s tempting to draw an analogy to couch potatoes watching television — and perhaps to future 3D VR addicts? — see comment by Johnny here: http://www.kurzweilai.net/ces-2013-hands-on-with-the-oculus-vr-rift-virtual-realitys-greatest-hope)
by Bri
Hmmmm…… Sounds like a substance abuse problem…… Maybe some public service announcements might be in order. How about this is your brain on sea water. This is your brain on rocks……. Just say no to rocks.
by RedQ
This sounds transformational—throw a molecular switch and cure the diseases of an aging brain. Based on track record, it’s unlikely to turn out to be of therapeutic value.