The results of their study are reported online in “Science Express” today, July 5, and will be published in an upcoming issue of “Science.”
Adult neural stem cells give rise to the three major types of brain cells – astrocytes, oligodendrocytes and neurons. Their role in producing neurons is of particular interest to scientists because neurons orchestrate brain functions -- thought, feeling and movement. If scientists could figure out how to create specific types of new neurons, they potentially could use them to replace damaged cells, such as the dopamine-producing neurons destroyed in Parkinson’s disease.
In recent years, scientists have determined that adult neural stem cells are located primarily in two regions of the brain -- the lining of the brain’s fluid-filled cavity, known as the subventricular zone, and a horseshoe shaped area known as the hippocampus. The laboratory of the senior author of the current study, UCSF’s Arturo Alvarez-Buylla identified the stem cells in the subventricular zone in 1999 (“Cell”, June 11, 1999).
While scientists have known that neural stem cells in the developing brain produce particular types of neurons based on where the stem cells are located in the embryo, studies carried out in cell culture have suggested that adult neural stem cells of the fully formed brain can give rise to many types of brain cells.
In the current study, conducted in mice, the team set out to explore whether neural stem cells in different locations of the subventricular zone are all the same. They did so using a method they developed to follow the fate of early neonatal and adult neural stem cells in 15 different regions of the subventricular zone. These cells typically produce young neurons that migrate to the olfactory bulb, where they mature into several distinct types of interneurons, neurons that are essential for the sense of smell.
To the team’s surprise, the adult neural stem cells in the various regions of the subventricular zone each gave rise to only very specific subsets of interneurons. Moreover, the stem cells were not susceptible to being re-specified. When they were taken out of their niche and transplanted into another region of the subventricular zone, they continued to produce the same subset of interneurons. Similarly, they retained their specialized production of distinct subtypes of neurons when removed from the animals’ brains and exposed to a cocktail of growth factors in a culture dish.
The findings, says the lead author of the study, Florian T. Merkle a graduate student in the Alvarez-Buylla lab, suggests that while adult neural stem cells of the subventricular zone can produce the three major types of brain cells -- astrocytes, neurons and oligodendrocytes – when it comes to neurons they seem to be specified, or programmed, to produce very specific subtypes.
“The data supporting the finding is remarkably clean and was highly unexpected,” says senior author Alvarez-Buylla, UCSF Heather and Melanie Muss Professor of Neurological Surgery. “We’ve been studying this region of the brain for many years and Florian’s data has produced a different scenario, so we have to readjust now.”
“We should abandon the idea that these cells are good for making any kind of neuron. This is just not going to be the case unless we find ways to reprogram these cells genetically.”
The insight, says Merkle, is a key step toward understanding the molecular mechanisms of neural stem cell potential. “Now you could compare adult stem cells in different regions at the genetic level. Since different neural stem cells make different types of neurons, maybe you could determine which genes are important for making, say, dopaminergic cells. In theory you could activate these genes in embryonic stem cells in the culture dish to try to create the desired type of neuron”.
The Alvarez-Buylla lab has identified neural stem cells in the adult human brain, but it is not known if these cells are heterogeneous. If human brains show a similar regionalization of stem cells, it might also be possible, says Alvarez-Buylla, to harvest them from the brains of patients, expand their numbers in the culture dish to obtain a particular neuron type, and transplant them back into patients.
Notably, the distribution of adult neural stem cells throughout the subventricular zone raises the possibility, he says, that the cells’ activity is regionally modulated in order to regulate the production of different types of neurons. “This may provide a mechanism for the brain to dynamically fine tune the olfactory bulb circuitry, raising a fascinating basic question about neuronal replacement: Why are so many different types of neurons, with such diverse origins, required for olfactory function"”
“The implication for cell-based therapies might be that it isn’t sufficient to replace one neuron,” he says. “You might have to replace combinations of different neuronal types when it comes to reestablishing neural function.”
The finding, he says, has not been without its hints. In 1996, the lab reported (PNAS, Dec. 1996) what he describes as “an amazing network of pathways” that collect adult neural stem cells from throughout the wall of the lateral ventricle of the subventricular zone.
“It’s taken us 10 years,” he says, “to figure out that these pathways reflect the transport of young neurons of different types born in unique locations.”
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences