Direct reprogramming

Scientists have turned human skin cells into motor neurons

Anna Kerman, XX2 century, based on the materials of Medicalexpress: Human skin cells transformed directly into motor neurons

Human motor neurons are difficult to study because they cannot be separated from a living patient. The motor neurons shown in the illustration are derived from skin cells of a healthy 42-year-old woman. Credit: Daniel Abernathy

Scientists have discovered a new way to directly transform human skin cells into motor neurons. This technology, developed at Washington University School of Medicine in St. Louis, will help physicians better understand diseases affecting motor neurons, in particular, amyotrophic lateral sclerosis (ALS).

Numerous groups of researchers are working on developing new ways to treat neurodegenerative diseases, but this is a difficult task, since it was previously impossible to grow human motor neurons in the laboratory. If the work of these neurons responsible for muscle contractions is disrupted, it causes diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy, which eventually leads to paralysis and death.

As a result of a new study, scientists from Washington University in St. Louis were able to turn skin cells taken from healthy adults directly into motor neurons, bypassing the stem cell stage. Thanks to this, it will now be possible to study human motor neurons in laboratories, which will significantly advance research. It is impossible to get a sample of these neurons from a living person, but it is easy to take a skin sample.

The study was published on September 7 in the journal Cell Stem Cell.

If we do without the stem cell stage, it will help to avoid ethical disagreements that arise when obtaining pluripotent stem cells – cells similar to embryonic cells, due to their ability to transform into any other cell. And, more importantly, as a result of using the new technology, motor neurons of the same age as skin cells can be obtained, which means the same age as the patient. Preserving the chronological age of cells is very important when studying neurodegenerative diseases that develop in people of different ages and progress over time.

"In our work, we used skin cells from healthy people aged 20 to 60 years," says senior author Dr. Andrew S. Yoo, associate professor of ontogenetics. – Our research has shown how RNA molecules interact with transcription factors and produce neurons of a certain type, in our case, motor neurons. In the future, we will study the skin cells of patients with motor neuron diseases. We will simulate the late stages of the disease using neurons obtained from patients."

Yu said: "Using the pluripotent cell stage in the work is like first destroying a house to the ground, and then building it again. What we are doing now can be compared to repairs: we are changing the environment, preserving the original structure – that is, the properties of adult neurons that need to be studied."

The ability to transform skin cells into other types of cells, for example, into neurons, will help to better understand the mechanism of diseases and find new ways to repair damaged tissues and organs.

To turn skin cells into motor neurons, the researchers exposed the cells to signaling molecules that are usually present in the brain in large quantities. Past studies have shown that exposure to two microRNA molecules (miR-9 and miR-124) transforms cells into neurons.

In the course of the new work, the scientists carefully studied the process of change, as they were interested in how to get neurons of a certain type. They found that the genes involved are turned on only if a certain combination of molecules is present. After many experiments with various combinations, the scientists found that if you add two more transcription factors (ISL1 and LHX3) to the already existing composition, then after about 30 days the skin cells turn into motor neurons of the spinal cord.

According to Dr. Yu and his co–authors, the combination of signals - miR-9 and miR–124 microRNAs plus ISL1 and LHX3 transcription factors - orders the cell to stop the processes characteristic of skin cells and deploy processes typical of motor neurons.

In one of the previous studies, Dr. Yu's team found that the combination of the same microRNAs and other transcription factors turns skin cells into other neurons – median striatum spike neurons that die in Huntington's disease.

The scientists said that in experiments on mice, the grown motor neurons are comparable in properties and functionality to ordinary ones. But it's hard to say if this is the case with human neurons. We need additional studies of samples of neurons obtained from patients who bequeathed the body to science.

Portal "Eternal youth" http://vechnayamolodost.ru  11.09.2017