Tuesday , January 26 2021

Scientists have grown Primate Brains-in-a-Dish on an unprecedented scale

We are not sure why that happened. Even when & # 39; is a topic of ongoing debate. But at some point our brains were for some reason great.

There are lots of hypotheses about how we came here, but to find supporting evidence, we need experiments on the brain of chimpanzees and humans, which involves practical (not to mention ethical) challenges. So these researchers went and built their own tests.

"It's a science fiction experiment that couldn't have happened ten years ago," says cell biologist Arnold Kriegstein of the University of California, San Francisco.

The team constructed simple, biochemically active brains from chimpanzee and human stem cells and used them to identify hundreds of genetic differences that could help explain their unique properties.

We are not just talking one or two here either. The researchers took cells from eight chimpanzees and ten people and used them to generate a population of 56 units, providing an unprecedented scope for accurate measurements.

Technically, the human and chimpanzee brains they developed in laboratory glass are not the fully developed clumps of wrinkled gray matter you would find inside a primate skull.

They are organoids – mixtures of tissues which are independently arranged in a 3D structure to act as a model of an organ.

While the line between an actual organ and its organoid derivative is unclear, it is clear that these cultures of neurological tissues cannot treat information as the real deal. But that's not the goal.

There is sufficient genetic and biochemical activity in these cultures to allow for experiments that would be impossible for bona fide samples.

Extracting DNA and proteins from the brain taken by deceased chimpanzees and humans and keeping them side by side is like comparing the final credits in two films. You may know the actors, but you are missing the plotters.

Brain organs allow researchers to measure how genes activate and biochemistry fluctuate, and the time of development of important cells and other structures.

Having dozens of organoids to compare means changes that are general to each species, can be selected with precision.

The researchers deconstructed their samples at different stages of development to compare the types of cells that appear and the genetic programs are activated at each stage.

These were all compared to reference materials taken from a third group of primates, rhesus monkeys.

Contrasts in the genetic activity of human and chimpanzee organs provide fruitful reasons for identifying important mutations in each species that could explain how our respective brains evolved.

"These chimpanzee organs give us an otherwise inaccessible window to six million years of our development," says neurologist Alex Pollen.

The analysis revealed 261 human-specific changes in genetic expression; One particular change that got their interest was a type of neural precursor.

Several years ago, Kriegstein's laboratory identified molecular traits of a kind of cell that gives rise to the majority of human cortical neurons, called an outer radial glial cell. This time, the team showed how the activity of these cells strengthened their participation in a human growth pathway and highlighted a pivotal shift that could help explain the branching of human development away from our great monkey relatives.

"Being so close to wild chimpanzees has prompted me to question the development of our own species," says Pollen, who had studied the development of fish near the Gombe Stream National Park's famous chimpanzee research facility.

"But first we needed genomes, stem cells and single-cell RNA sequencing to understand the evolutionary programs that drive brain development in the two species."

Whatever the story lies behind the exceptionally expanded minds of humans and their ilk, it becomes complex. Organoids provide new ways to study such activity on an unprecedented scale, which is the basis for showing how small changes in our evolutionary past have led to great differences in our biology.

This research was published in Cell.

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