Neurons made from blood cells – a new tool for understanding brain diseases

June 8, 2018 by Marius Wernig, The Conversation

Marius Wernig, Thomas C. Südhof and their colleagues created these “Induced neuronal (iN) cells” from adult human blood cells. Credit: Marius Wernig, CC BY-ND
Our team at Stanford University has just figured out the recipe for converting blood cells from adults directly into nerve cells, or neurons.

You may be wondering why anyone would want to convert blood into brain . Researchers like myself would like to gain a better understanding of what causes brain diseases such as autism, schizophrenia or major depression. But it is difficult to study complex diseases like these in the lab.

Our new procedure should make this research easier because we can collect blood cells from a patient with schizophrenia, for example, and see whether processes that happens in an individual's brain can be replicated in blood-derived neurons in the petri dish. This research will not only provide insights into how diseases develop but will also create a way to test new therapies before they are given to .

Why are neuropsychiatric diseases so difficult to study?

What makes brain diseases hard to study is that every person has a unique genetic makeup which means that the same disease – autism or schizophrenia or depression – manifests differently in every individual. In addition, only a small percentage of patients have mutations in a single gene that appears to be responsible for the disease.

When the DNA of hundreds of patients with neuropsychiatric diseases and healthy individuals was screened for disease-causing , certain versions of genes were more common in patients versus the healthy population, suggesting they may play a role in causing the disease.

This suggests that the majority of patients carry multiple genes that all contribute to their condition. The contribution of each gene is small, but the combination of dozens of genetic variations add up to a severe disease.

For this reason, it is challenging to assess the role of these minor genes in the whole disease process, figure out which ones are key players and determine the critical combination of genetic variations necessary to trigger disease. Because we don't know the key genes involved, we cannot engineer mice that accurately mimic the disease process in humans, and we can't test therapies to address these illnesses.

Reprogramming the cell

Cellular reprogramming, the ability to convert one cell type into another, offers a possible solution to this problem. In 2006, scientists showed that could be transformed into pluripotent stem cells – cells that have the potential to develop into many cell types – which in turn could be coaxed into neurons. A few years later, in 2010, we simplified this two-step process and discovered a way to convert skin cells directly into neurons.

But obtaining skin cells is not straightforward and involves a painful procedure. Moreover, the skin cells have to be grown before they are converted into other cells, which can introduce artificial mutations not relevant to causing the disease.

With our approach, we can take just a few drops of blood and generate tens of thousands of neurons.

We can complete this shape-shifting transformation of one cell type into another by adding just four specific proteins – which we determined play vital roles in brain development – to freshly drawn or stored blood cells. These four factors are enough to rapidly reprogram these cells and transform them into neurons within a few weeks of treatment.

Over this period the white change shape, from a ball-shaped cell to a neuron with delicate tentacle-like branches. They display proteins that typically decorate the surface of neurons, and in our experiments they behaved like neurons and transmitted electrical signals. Compared to neurons in the brain the "induced" neurons appear less mature. Our technique is already useful for some applications, for others that require mature neurons it still needs to be refined.

Our strategy allows scientists to generate neurons from patients affected with a disease of interest which harbor all the genetic elements that actually cause the condition. We will still need to create from many patients and healthy subjects and analyze the genes that are active in each group before we can determine which genes are involved in all forms of the disease. Through this method, we will be hopefully be able to identify the most relevant genes which should be good targets for disease-modifying medicines.

Explore further: Researchers transform human blood cells into functional neurons

Related Stories

Researchers transform human blood cells into functional neurons

June 4, 2018
Human immune cells in blood can be converted directly into functional neurons in the laboratory in about three weeks with the addition of just four proteins, researchers at the Stanford University School of Medicine have ...

Interconnected cells-in-a-dish let researchers study brain disease

May 3, 2018
By creating multiple types of neurons from stem cells and observing how they interact, Salk scientists have developed a new way to study the connections between brain cells in the lab. Using the technique, which generates ...

Impaired energy production may explain why brain is susceptible to age-related diseases

May 29, 2018
Defective energy production in old neurons might explain why our brains are so prone to age-related diseases. Salk researchers used a new method to discover that cells from older individuals had impaired mitochondria—the ...

Neurons derived from super-obese people respond differently to appetite hormones

April 19, 2018
US scientists have successfully generated hypothalamic-like neurons from human induced pluripotent stem cells (hiPSCs) taken from the blood and skin cells of super-obese individuals and people with a normal body weight. The ...

Altering Huntington's patients' skin cells into brain cells sheds light on disease

February 5, 2018
Scientists at Washington University School of Medicine in St. Louis have transformed skin cells from patients with Huntington's disease into the type of brain cell affected by the disorder. The resulting mass of neurons serves ...

Conversion of brain cells offers hope for Parkinson's patients

April 11, 2017
Researchers at Karolinska Institutet have made significant progress in the search for new treatments for Parkinson's disease. By manipulating the gene expression of non-neuronal cells in the brain, they were able to produce ...

Recommended for you

Scientists identify critical cancer immunity genes using new genetic barcoding technology

October 20, 2018
Scientists at Mount Sinai have developed a novel technology for simultaneously analyzing the functions of hundreds of genes with resolution reaching the single cell level. The technology relies on a barcoding approach using ...

A single missing gene leads to miscarriage

October 19, 2018
A single gene from the mother plays such a crucial role in the development of the placenta that its dysfunction leads to miscarriages. Researchers from the Medical Faculty of Ruhr-Universität Bochum (RUB) have observed this ...

Making gene therapy delivery safer and more efficient

October 18, 2018
Viral vectors used to deliver gene therapies undergo spontaneous changes during manufacturing which affects their structure and function, found researchers from the Perelman School of Medicine at the University of Pennsylvania ...

Student develops microfluidics device to help scientists identify early genetic markers of cancer

October 16, 2018
As anyone who has played "Where's Waldo" knows, searching for a single item in a landscape filled with a mélange of characters and objects can be a challenge. Chrissy O'Keefe, a Ph.D. student in the Department of Biomedical ...

Researchers use brain cells in a dish to study genetic origins of schizophrenia

October 16, 2018
A study in Biological Psychiatry has established a new analytical method for investigating the complex genetic origins of mental illnesses using brain cells that are grown in a dish from human embryonic stem cells. Researchers ...

Why heart contractions are weaker in those with hypertrophic cardiomyopathy

October 16, 2018
When a young athlete suddenly dies of a heart attack, chances are high that they suffer from familial hypertrophic cardiomyopathy (HCM). Itis the most common genetic heart disease in the US and affects an estimated 1 in 500 ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.