A Genetic Map Hints At What Makes A Brain Human

Nov 16, 2015
Originally published on November 18, 2015 12:28 pm

Patterns of gene expression in human and mouse brains suggest that cells known as glial cells may have helped us evolve brains that can acquire language and solve complex problems.

Scientists have been dissecting human brains for centuries. But nobody can explain precisely what allows people to use language, solve problems or tell jokes, says Ed Lein, an investigator at the Allen Institute for Brain Science in Seattle.

"Clearly we have a much bigger behavioral repertoire and cognitive abilities that are not seen in other animals," he says. "But it's really not clear what elements of the brain are responsible for these differences."

Research by Lein and others provides a hint though. The difference may involve brain cells known as glial cells, once dismissed as mere support cells for neurons, which send and receive electrical signals in the brain.

Lein and a team of researchers made that finding after studying which genes are expressed, or switched on, in different areas of the brain. The effort analyzed the expression of 20,000 genes in 132 structures in brains from six typical people.

Usually this sort of study is asking whether there are genetic differences among brains, Lein says.

"And we sort of flipped this question on its head and we asked instead, 'What's really common across all individuals and what elements of this seem to be unique to the human brain?' " he says.

It turned out the six brains had a lot in common.

"One of the big findings of the paper is that whereas there's a lot of very, very small variation, on the grand scale in the brain there's only a limited number of patterns," says Mike Hawrylycz, another Allen Institute investigator and lead author of the paper, which appears in Nature Neuroscience.

The team first identified 32 of the most common genetic expression patterns. And they found that the genes that were least likely to vary from person to person included those known to be associated with diseases such as epilepsy, autism, Parkinson's and Alzheimer's.

The expression patterns also revealed genes that haven't yet been linked to a brain disease, but are likely candidates.

Then the team compared expression patterns found in people with those found in mice. "And it turns out that the patterns which are typically most associated with some of these diseases are not really well recapitulated in the mouse," Hawrylycz says.

The discrepancy could help explain why brain drugs that work in mice often fail in people.

The comparison of mouse and human gene expression patterns also found a difference involving glial cells. "The patterns that are more related to the neurons, the sort of information carriers in the brain, tend to be better conserved across species," Lein says. "Those that are related to the support cells, the glial cells, are actually less conserved. This was somewhat of a surprise."

But not a complete surprise. For a long time scientists believed glial cells weren't involved in higher brain functions, like thought. In recent years, though, a number of studies have suggested that glial cells, and especially a star-shaped variant called an astrocyte, play an important role in learning and intelligence.

"We've spent a lot of years studying the function of glial cells using the mouse brain as a model system," says Ben Barres, a professor of neurobiology at Stanford School of Medicine. "And we've found, to our great surprise, that the glial cells are actually much more active in controlling neural circuits in the brain than people had generally thought."

Research from Barres' lab has already shown that astrocytes help determine when and where neurons make connections in the mouse brain. And the lab has begun studying astrocytes in the human brain.

But that's difficult. "It's actually very hard to get human brain material that's in sufficiently good condition to study," Barres says.

He says he's confident that scientists will eventually find out what makes the human brain different. But they may have to employ a new technique, he says, which uses stem cells to grow miniature human brains in the lab.

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ARI SHAPIRO, HOST:

Researchers have created a new, highly detailed map of the human brain. This map doesn't feature the brain's anatomy. It shows which genes are expressed in different areas. NPR's Jon Hamilton reports it provides some hints about what makes the human brain special.

JON HAMILTON, BYLINE: Scientists have been dissecting human brains for centuries. But Ed Lein of the Allen Institute for Brain Science in Seattle says they still haven't explained abilities like using language or solving complex problems.

ED LEIN: Clearly, we have a much bigger behavioral repertoire and cognitive abilities that are not seen in other animals, but it's really not clear what elements of the brain are responsible for these differences.

HAMILTON: So Lein and a team of researchers have been looking at which genes are expressed or switched on in different areas of the brain. They studied brains from six typical people. Lein says usually this sort of study asks about differences across the brains.

LEIN: And we sort of flip this question on its head. And we asked, instead, you know, what's really common across all individuals, and what elements of this seem to be unique to the human brain versus being more general to all mammals, let's say?

HAMILTON: And it turned out the six brains had a lot in common. Mike Hawrylycz of the Allen Institute is lead author of the paper which appears in Nature Neuroscience

MIKE HAWRYLYCZ: One of the big findings of the paper is that whereas there's a lot of very, very small variation on a grand scale in the brain, there's only a limited number of patterns that these genes take.

HAMILTON: The team identified 32 of the most common genetic expression patterns. Then they compared the patterns in people with those in mice. And they found something that could help explain what makes human brains so different. Ed Lein says it involves neurons and another type of brain cell called the glial cell.

LEIN: The patterns that are more related to the neurons, the sort of information carriers in the brain, tend to be better conserved across species, whereas those that are related to the support cells, the glial cells, are actually less conserved. This is somewhat of a surprise.

HAMILTON: A surprise because scientists used to think glial cells weren't involved in higher brain functions like thought. But recent studies have suggested that glial cells, and especially a star-shaped variant called astrocytes, play an important role in learning and intelligence. Ben Barres is a professor of neurobiology at Stanford University.

BEN BARRES: We've spent a lot of years studying the function of glial cells using the mouse brain as a model system. And we've actually found, to our great surprise, that the glial cells are actually much more active in controlling neural circuits in the brain than people have generally thought.

HAMILTON: Barres says research in his lab has shown that astrocytes help determine where and when neurons make connections in the mouse brain. And he's begun studying astrocytes in the human brain, but he says that's difficult.

BARRES: It's actually very hard to get human brain material that's in sufficiently good condition to study it. And so as soon as the tissue is removed from the body, it starts to degrade.

HAMILTON: Barres thinks scientists will find out precisely what makes a human brain different, but he says they may have to employ a new technique. It uses stem cells to grow miniature human brains in the lab.

There's one more thing the new research turned up. It's a possible explanation why so many brain drugs that work in mice don't help people. Mike Hawrylycz of the Allen Institute says that among the genes that varied the least in those six human brains were those associated with diseases such as epilepsy, autism and Alzheimer's. So Hawrylycz says they looked for these same patterns in mice.

HAWRYLYCZ: And it turns out that the patterns which are typically most associated with some of these diseases are not really well recapitulated in the mouse.

HAMILTON: The mouse brains didn't have those gene patterns. So future drug testing may include those miniature human brains grown in the lab. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.