Organoids offer clues to how brains are made in humans and chimpanzees

Brainlike clumps of cells reveal similarities and differences among primate brain development

Cerebral organoids made of human cells (left) or chimpanzee cells (right)

Cerebral organoids made of human cells (left) or chimpanzee cells (right) contain nerve cells in different stages of maturity (green indicates cells that will go on to form nerve cells).

S. Kanton et al/Nature 2019

Brainlike blobs made from chimpanzee cells mature faster than those grown from human cells.

That finding, described October 16 in Nature along with other clues to human brain development, is one of the latest insights from studies of cerebral organoids — three-dimensional clumps of cells that can mimic aspects of early brain growth (SN: 2/20/18).

The new study “draws interesting parallels, but also highlights important differences” in the way that the brains of humans and chimpanzees develop, says Paola Arlotta, a neurobiologist at Harvard University who was not involved in the study. While “it’s still early days in the organoid world,” the results represent an important step toward understanding the particulars of the human brain, she says.

To make cerebral organoids from chimpanzees, researchers use cells in blood left over from veterinarians’ routine blood draws. In the vials were white blood cells that could be reprogrammed into stem cells, which themselves were then coaxed into blobs of brain cells. “From that, we get something that really looks a lot like the early brain,” says Gray Camp, a stem cell biologist at the Institute of Molecular and Clinical Ophthalmology Basel in Switzerland.

There were no obvious differences in appearance between the chimpanzee organoids and the human organoids, Camp says. But a close look at how genes behaved in the two organoids — and how that behavior changed over time — turned up a big difference in pacing. Chimpanzee organoids seemed to grow up faster than their human counterparts.

At the same point in time, chimpanzee nerve cells, or neurons, were more mature than human neurons, possessing a profile of gene behavior that’s known to come with cellular age, the researchers found. That lag was “striking,” Camp says. Compared with other species, human brains are known for taking a long time to grow up, maturing through early life well past adolescence — a sluggish pace captured by the organoids.

Aligning those different timelines of growth allowed researchers to find genes that behaved differently in the two species, beyond simple timing differences. Other analyses turned up differences in how stretches of DNA were used. Some stretches are missing in people, but present in chimpanzees and other primates. And in chimpanzees, those areas appeared poised for action, perhaps ready to influence the behavior of certain genes, Camp says.

Although the human and chimp organoids offer clues about early brain development in primates, the brain blobs are still approximations of the real thing. Human brain organoids, for example, haven’t yet been able to capture a key trait of the human brain — its big neocortex, the outer layer of the brain involved in complex thinking, Camp says. Nor do these organoids re-create sophisticated connections between brain regions. Still, advances are coming fast (SN: 8/29/19). Studies of organoids hold promise, particularly for their ability to reveal developmental processes that would otherwise be hidden, such as the brain’s earliest days as it develops in the womb, Arlotta says.

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