Stem cells are incredible, and combined with gene editing techniques like CRISPR, it seems like there’s almost nothing you can’t just whip up in a lab. Tiny, folded blobs of brain tissue, for example.
A group of scientists from MIT, Harvard, and the Austrian Academy of Sciences didn’t grow the blobs pictured above for fun, though. They’re figuring out new ways to study how brains develop, and even used their latest brain blobs to study the effects of Zika virus - a disease notorious for attacking the developing brains of infants. But the big takeaway from the research, which was published in the journal Cell Stem Cell last week, was finding a hack that makes it easier to develop a realistic model of the human brain.
The study started with human embryonic stem cells, which that can differentiate into many different types of cells. The scientists had a hunch that altering a certain set genes would change the way brains developed. So they used CRISPR to delete the PTEN gene—short for the protein it makes, phosphatase and tensin homolog—out of some of the stem cells and grew each set into organoids, little pieces of brain tissue. The organoids with PTEN grew into smooth little brainlets, while those without the PTEN protein grew larger and even started developing folds (larger is relative; the blobs were only a few millimetres big). Organoids grown from PTEN-less mouse stem cells, meanwhile, grew larger but didn’t develop folds.
The team saw a use for their mutant pieces of brain tissue: studying Zika virus. Hacking the stem cells’ genomes allowed the researchers to create more complex and human-like models of neural cortex tissue, which could then be used to understand the effects of diseases on the brain. The introduction of the Zika virus right at the time of folding limited both the growth of the organoid and the amount of folding. The introduction of dengue did not cause the same effect.
Studying brain development is difficult, said the study’s authors, because it’s hard to get hold of foetal brain tissue. Plus, the authors point out that their current brain organoid system requires deleting the PTEN gene to get folds in their mini-brains—meaning that the model isn’t a perfect representation of a human brain which has that gene intact. Nevertheless, this work reveals the importance of certain proteins in regulating brain growth and development, and the hack allowed scientists to control and study specific parts of the organoid’s development and explore how factors like Zika might interact.
Also, the little brain blobs look awesome and super gross. [Cell Stem Cell]