Can this research help scientist better understand brain developement and what goes wrong in autistic brains?
Emerging tools and techniques that may advance autism research
Baby brain: Novel lab-grown ‘mini-brains’ mimic specific regions of the human brain; they contain both neurons (green) and support cells called glia (purple).
Photographs courtesy of Fikri Birey, Pasca Laboratory, Stanford University
Two new methods for building ‘mini-brains’ may help researchers study how early brain development differs in people with autism.
One method enables scientists to recreate specific brain regions rather than an entire brain1. The other reduces the time and cost to make a mini-brain, promising to boost sample sizes from a few organoids per study to hundreds2.
Scientists typically make brain organoids by transforming cells from a person’s skin, blood or urine into stem cells capable of turning into almost any cell type. They then use chemicals to transform the stem cells into brain-cell precursors, and let them mature.
The resulting mixture of cells is often unpredictable, however, so it does not mimic the composition of any particular brain region.
In one of the new studies, researchers created mini-brains that resemble either the dorsal forebrain or the ventral forebrain, two regions of the developing brain.
The researchers use a multi-step process: They coax stem cells to become brain-cell precursors in a standard way. They then use a chemical cocktail to shape the precursors into a specific mixture of cells characterizing either the dorsal or ventral forebrain.
The brain-like blobs can be kept alive for more than two years, maturing long enough to develop the cell types, activity patterns and gene-expression profiles of a typical human brain after birth.
The researchers allow the mini-brain regions to fuse by suspending two of them in the same tube. The fusion enables researchers to study how brain regions form connections and communicate. The report was published in September in Nature Protocols.
Emerging connections: Fusing mini-brains in culture may reveal how brain regions interact in early development.
Pasca Laboratory, Stanford University
The approach may also help reveal how neurons’ migration goes awry in autism.
Neurons that dampen brain activity in the ventral region typically travel to dorsal areas during brain development. In autism, these inhibitory neurons do not migrate properly3. The fused mini-brain regions may help researchers better understand this movement and how it differs in autism.
In a separate study, scientists drastically cut the time it takes to build a mini-brain. The researchers discovered that they could boost the proportion of stem cells that mature into brain cells if they started transforming the cells earlier — after letting
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