2023-09-13 22:11:00
Photomicrograph of a human brain organoid, with cells with genetic mutations shown in red. Genes involved in autism can be identified at once by causing different mutations in multiple cells at the same time. / Institute for Molecular Biotechnology (IMBA), Austrian Academy of Sciences
A path has been opened to identify brain genes that cause autism at once. Until now, experimental animals with specific genetic mutations have been created and their functions studied separately. In other words, 8-lane and 10-lane highways have been opened for brain genetic research that used to only have one-lane roads. It is expected that it will be of great help in finding the cause and treatment of autism by being able to identify genes involved in brain development much more quickly.
A joint research team led by Dr. Juergen Knoblich and Dr. Chong Li from the Institute for Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences and Professor Barbara Treutlein from ETH Zurich (ETH) in Switzerland conducted an international conference on the 14th. “We have developed a method to simultaneously investigate the functions of genes involved in autism by inducing mutations in each of the genes involved in autism using brain organoids,” he wrote in the academic journal Nature.
Organoids are stem cells cultured into a three-dimensional structure similar to an organ, and are called mini organs. Previously, human cells were grown in flat petri dishes, which did not properly reflect the inside of the human body. Brain organoids are like mini brains made from stem cells.
◇Causes different genetic mutations in each cell of the mini brain
Researchers found that the human brain develops differently from other animals. The human brain has a layered structure of cortex. Because of this, there are more cases where neural development is not done properly. A typical example is autism (ASD), which has difficulty getting along with others and difficulty communicating verbally.
Scientists have discovered several gene mutations involved in autism, but it has been difficult to understand how these genes cause abnormalities in brain development. This is because experimental animals show brain development patterns that are different from humans. “Only experimental models of the human brain can reproduce the complexity and specificity of the human brain,” said Dr. Knoblich.
The research team developed a technology called ‘CHOOSE (CRISPR-human organoids-scRNA-seq)’ to simultaneously examine genes involved in autism in the human mini brain. CRISPR is an English translation that means decoding (seq) the function of genes (scRNA) of individual cells in human organoids using CRISPR gene scissors that can cut out desired genes. Using CRISPR gene scissors, mutations are induced in different genes in each brain organoid cell, and the results are analyzed at once.
The researchers announced that they analyzed 36 autism-related genes simultaneously using this method. The Austrian researchers were responsible for cultivating brain organoids and genetic mutations, while the Swiss researchers analyzed extensive information on the operation of various genes using an artificial intelligence computer. The researchers said they identified cells that are more prone to problems during brain development and identified a network of cells that are vulnerable to mutations that cause autism.
Dr. Jürgen Knoblich of the Austrian Institute for Molecular Biotechnology (IMBA) is explaining while looking at a microscopic picture of a human brain organoid./Institute for Molecular Biotechnology (IMBA), Austrian Academy of Sciences
◇ Research that would take dozens of doctors and several years can be done by one person at once
Until now, in order to find out the function of genes involved in brain development, each mouse with a mutation in the corresponding gene had to be obtained. Now, it is possible to study multiple genes simultaneously with a single mini brain, without the need for mice. Koo Bon-kyung, director of the Institute for Basic Science (IBS) Genome Editing Research Center, said, “What might only be studied at the mouse brain level even following dozens of postdoctoral researchers studied for years, is now possible for one postdoctoral researcher to research in a human brain model at a time.” “He said.
The researchers confirmed whether the genetic mutation identified in the mini brain actually causes autism. First, brain organoids were created using stem cells collected from two autism patients. Autism brain organoids showed defects in specific cells. The researchers confirmed that such a defect actually occurred in brain images taken when one patient was a fetus.
Dr. Knoblich said, “The technology we developed this time will be widely applied to study various disease-related genes beyond brain organoids,” adding, “It will greatly help in identifying the process of disease development by greatly reducing the analysis time for scientists and doctors.” “I can give it to you,” he said.
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