The SfN Presidential Lectures are always given by amazing scientists and Sunday night's presentation by Dr. Paola Arlotta was no exception. In case you missed her talk on "Understanding Brain Development: from Embryos to Organoids" here is a brief summary. Her talk was broken into two categories: how the brain establishes cellular diversity and growing 3D human brain organoids outside the embryo.
Dr. Arlotta built upon the Allen Institutes work to classify neuron types in the cerebral cortex and genetic markers for those classifications. It was found that most neurons do not have a single gene marker but rather signature gene groups. As the cerebral cortex grows from prenatal through adolescence cells differentiate in groups, not linearly. One cell does not become all cell types, but rather there are “decision points” that lead to branching of only subset of cell types from that point forward.
Dr. Arlotta’s group focused on identifying what happens at these decision points in order to force progenitors to become specified neurons. They worked on isolating selected cell types and identifying which gene molecules were co-regulated. They then determined which progenitor cells changed when given these gene molecules in vivo.
However, most genetic neurodevelopmental diseases are more complex than single cell types. To address this the Arlotta group began working on developing 3D human brain organoids. They used human blood and skin cells to form iPSCs. iPSCs were then grown into 3D spheres about 4-5mm that could live up to 9 months, much longer than typical iPSCs. These organoids will self-organize. Within the organoids, cell diversity similar to human brain could be observed. Ventricles, sub-ventricle, and cortical regions were all identified.
They did begin to find that there was a large amount of variability between organoids. Work by Silvia Vaclasco began to show that after 3 months the cell diversity was indeed reproducible. By 6 months astrocytes could be identified. Most excitingly the gene profiling from these organoids matched that of a human brain. Dr. Arlotta concluded “organoids can serve as reductionist experimental model of human brain development,” and help us study patients with diseases we cannot model in animals. We can also use this method to produce patient-derived iPSCs and begin to identify molecular pathways and treatments for more complex diseases.
If you missed this talk, the largest missing component was Dr. Arlotta’s passion for science. She shared slides just to ensure that all this differentiation is available in the genome. We all know that all cells have the same DNA and therefore the same information. But to hear Dr. Arlotta remind us that these human organoids started as skin cells was mind-blowing. Science can be epically cool sometimes, and this lecture was a great example of that.