Brain research with organoids
Scientists develop effective method to genetically modify brain organoids
Lidiia Tynianskaia
Brain organoids are grown in the laboratory from so-called induced pluripotent stem cells. These cells are usually derived from skin or blood cells that are "reprogrammed" beforehand. That is, they are modified so that they regress to stem cells and can then differentiate into any other cell type, such as neurons.
"We are particularly interested in the genetic factors underlying brain development in primates," explains Michael Heide, head of the Junior Research Group Brain Development and Evolution at DPZ and author of the study. "The brain organoids allow us to reproduce these processes in the Petri dish. To do that, however, we need to genetically modify them."
Until now, these procedures were sometimes very labor-intensive and took several months. The team of researchers led by Michael Heide has now developed a method that allows brain organoids to be genetically manipulated quickly and cost-effectively.
"We use microinjection and electroporation for our method," Heide explains. "In this process, genetic material is injected into the organoids with a very thin cannula and introduced into the cells with the help of a small electrical pulse. It takes only a few minutes, and the brain organoids can be analyzed after a few days."
Plasmids are used to insert the genetic material. These are circular pieces of DNA that contain the gene of interest. In the feasibility study, the researchers used the green fluorescent protein (GFP) gene for this purpose. Successfully modified cells in brain organoids thus glow green under fluorescent light.
"The method is equally suitable for brain organoids from humans, chimpanzees, rhesus macaques and common marmosets," Heide summarizes. "This allows us to perform comparative studies on physiological and evolutionary brain development in primates and is also an effective tool to simulate genetically caused neurological malformations without having to use monkeys in animal experiments."
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