A new study from UCLA and Stanford University researchers finds that three-dimensional ‘micro-brain’ organoids can come from mature human cells in a way that is very similar to human brain development.
For the new study, published in Ignorance of nature February 22, senior authors Dr Daniel Geschwind of UCLA and Dr Sergiu Pasca of Stanford University performed an extensive genetic analysis of organoids grown for up to 20 months in a lab basin. They found that these 3D organs follow an internal clock that directs the maturation in line with the human development timeline.
“This is a novel -; So far, no human has grown and characterized these organs for this time, and they have not been shown to rebalance human brain development. in a laboratory environment for the most part, “said Geschwind, MD, PhD, the distinguished MacDonald Professor of Human Genetics at UCLA ‘s David Geffen School of Medicine, a member of the Eli and Edythe Broad Center for Regenerative Medicine and Gas Research -cell at UCLA, and the associate senior dean and associate vice-chancellor and director of the Institute for Precision Health at UCLA.
“This will be an important stimulus for the field. We have shown that these organs can mature and reproduce many aspects of normal human development – making them a good model for the study of human disease in a basin, “he said.
Human brain organoids are formed using stimulated pluripotent stem cells, also called iPS cells, which are derived from skin or blood cells that have been reprogrammed back into an embryonic gas cell-like state allowing scientists to create any cell type.
These iPS cells are then viewed with a specific combination of chemicals that affect them to form a cell in a specific region of the brain. With the right time and conditions, the cells organize themselves to create 3D structures that faithfully reproduce many aspects of human brain development.
Organs derived from human cells have the potential to transform the use of medicine by giving researchers unprecedented insights into how complex organs – including the brain – – developing and treating disease.
For several years, researchers have been developing human brain organoids to study human brain and neurodevelopmental disorders, such as epilepsy, autism and schizophrenia.
The usefulness of these models has been hampered by the widespread belief that the cells that make up these organs are still stuck in a developmental state similar to the cells seen in fetal development. The study shows that the cells may be able to grow to maturity allowing scientists to better diagnose adult-onset diseases, such as schizophrenia or depression.
There is great interest in gas cell models of human disease. This work represents an important milestone in showing which aspects of human brain development are modeled with the highest fidelity and which specific genes behave well in vitro and when it is best to model them. Equally important, we provide a framework based on neutral genomic analyzes for assessing how well in vitro models model in vivo development and function. “
Geschwind, MD, PhD, Distinguished MacDonald Professor, Human Genetics, David Geffen School of Medicine, UCLA
The authors also provide a tool called GECO that allows researchers to study their genes of interest for measuring brain fidelity in vitro and in vivo.
“We show that these 3D brain organs follow an internal clock, which takes place in a laboratory environment in parallel with what is happening within growth -live, “said first author Aaron Gordon, PhD, doc post in the Geschwind Lab at UCLA ‘s David Geffen School of Medicine.” This is a remarkable discovery -; we show that they reach the stage of postnatal maturity by about 280 days in culture, after which begin to model parts of the baby’s brain, including known physical changes in it the neurotransmitter signaling. “
University of California, Los Angeles (UCLA), Health Sciences
Gordon, A., et al. . Ignorance of nature. doi.org/10.1038/s41593-021-00802-y.