Another way to directly convert fibroblasts into neurons
You can get neurons directly from skin cells using microRNALifeSciencesToday based on Stanford School of Medicine:
Efficient process using microRNA converts human skin cells into neurons, study shows
Adding two microRNAs to the usual genetic material of skin cells is enough to turn these cells into fully functional neurons, bypassing the stem cell stage, according to scientists at Stanford University School of Medicine (Stanford University). The discovery, published in the journal Nature, is one of the few recent reports on methods for obtaining human neurons in the laboratory.
Immunofluorescence micrography of fibroblast.
Fibroblasts are cells that give rise to connective tissue,
for example, the main structural protein of the body – collagen.
The cell nucleus containing genetic information is lilac.
Microtubules – protein filaments that make up part of the cytoskeleton – are red.
The cytoskeleton maintains the shape of the cell, allows the cell to move
and takes part in the intracellular transport of substances.
(Photo: Dr. Jan Schmoranzer/Science Photo Library)
The new opportunity to grow neurons from scratch is a big step forward in the field of neurobiological research, which has reached a dead end due to the lack of human neurons. Unlike skin cells or blood cells, neurons cannot be attributed to something that the human body can easily give up for the sake of scientific research.
Gerald Crabtree, MD, Professor of Pathology and Developmental Biology at Stanford University School of Medicine (Photo: med.stanford.edu )
"The main problem in neuroscience remains the lack of a good human model," says Gerald Crabtree, MD, professor of pathology and developmental biology, senior author of the study. "Neurons are not blood. It's not something people would be willing to sacrifice."
Obtaining neurons from easily accessible cells, such as skin cells (fibroblasts), makes it possible to develop new ways to study their development, simulate diseases of the nervous system and test methods of their treatment.
In addition, the availability of neurons will help to move forward in attempts, still in their infancy, to replace damaged or dead neurons with new ones.
Two years ago, before successfully obtaining neurons directly from skin cells, scientists discovered that the same result can be achieved if you first transform a skin cell into a stem cell, and then "persuade" the stem cell to become a neuron. But a new study by Crabtree and two other papers have shown that the transformation of a skin cell directly into a neuron, without the "pit stop" of a stem cell, is quite possible.
Among other works, Crabtree's research occupies a special place because of the amazing nature of the molecules that "push" the cell to transform - short chains of genetic material called micro RNAs, well known for their ability to bind to specific genetic transcripts and suppress their activity. "In this case, however, they act as instructions," explains Crabtree.
Scientists learned about the ability of microRNAs to switch the direction of cell development when Andrew Yoo, PhD, then a postdoctoral fellow in Crabtree's laboratory, tried to figure out what makes a neural stem cell differentiate into a mature neuron. He found that the main role in this process is played by two microRNAs, miR-9/9* and miR-124, which control the molecular mechanism (the so-called chromatin-remodeling complex BAF), which arranges chromosomes in such a way that the cell remains stem.
"When miR-9/9* and miR-124 microRNAs bind to one of the subunits of the 13-component chromatin-remodeling complex BAF, they turn off this function, and cells begin to grow and contact each other, that is, they become mature functioning neurons," explains Dr. Crabtree. After publishing this discovery in Nature in 2009, Dr. Yu continued his work trying to understand how these two micro RNAs function. In particular, he decided to find out what would happen if they were introduced into cells in which they are usually absent.
At first, he didn't even believe what he saw under the microscope: cells with additional microRNAs injected began to look like neurons. "It was very strange. We were just amazed," recalls Professor Crabtree.
Dr. Yu, one of the lead authors of the new paper, continued to study this phenomenon with his colleagues from Stanford. Using a virus to deliver microRNA to skin cells, the scientists tested whether the resulting cells were really neurons. They found that from 2 to 3 percent of skin cells were reliably transformed into neurons: the cells generated electrical signals used by neurons to interact with each other, and secreted so–called synaptic vesicles - that is, they did everything that mature neurons usually do.
"What we got are neurons characteristic of the frontal cortex. These are the neurons that seem to be the hardest to get. These are the neurons that allow us to think, which we use to compare things and see connections between them, and not those that are involved in evolutionarily earlier emotional reactions," says Dr. Crabtree. "In addition, among the transformed cells, we found inhibitory (inhibitory) neurons, whose function is to keep other neurons in a resting, controlled state."
By adding two factors used in similar experiments by their colleague Marius Wernig, the scientists increased the efficiency of transformation to 20 percent. Doctor of Medicine Marius Wernig is the author of the first publication on the direct transformation of human skin cells into neurons. In May of this year, Dr. Wernig reported in the journal Nature that a combination of four special proteins can directly transform skin cells into functional neurons with an efficiency of 2 to 4 percent. (More recently, on July 3, the same journal Nature published a study led by a scientist from the San Raffaele Scientific Institute in Milan, Italy, showing that a combination of three other proteins can also induce transformation).
"We've been going for this success for a long time," says Crabtree. "This study is finished, but there is still more work ahead, and everything suggests that there are not only different ways to get neurons, but also the possibility of getting different types of them."
In Wernig's study, the same "thinking" neurons were obtained, but no inhibitory ones were found. The Italian group obtained neurons that produce dopamine, a chemical that influences many behavioral reactions – from movement and learning to sleep.
Among the projects based on the results of this study is an attempt to create a model of Down syndrome. Stanford graduate student Alfred Sun obtained skin cells from such patients and transformed them into neurons. Now he is trying to understand how they differ from normal ones.
"We believe that there are certain biochemical deviations that can be corrected," comments the first results of Crabtree's new work.
The study was funded by the National Institutes of Health of the USA, Howard Hughes Medical Institute and the Department of Pathology of Stanford University (Stanford's Department of Pathology).
Portal "Eternal youth" http://vechnayamolodost.ru18.07.2011