Oct 14, 2023 - Science

New brain map reveals thousands of cell types

Illustration of a brain under a microscope.

Illustration: Shoshana Gordon/Axios

Scientists now have a census of the cells in the human brain — a key step in creating a detailed map of the organ where our thoughts, movements and emotions originate.

Why it matters: Scientists say this parts list — combined with information still to be gleaned about the circuits they form — will help provide much-needed insights into diseases and disorders that affect the brain.

How it works: Researchers studied 100 tissue samples from different regions across the human brain and analyzed the RNA in millions of individual cells to see which genes in the brain were being expressed to make different proteins in the cell.

  • Other teams looked at how different chemical modifications regulate that expression.
  • Using the information and knowing roughly where in the brain the samples were taken, researchers created the first reference map of the human brain.
  • Teams of scientists around the world conducted similar analyses of cells from the brains of mice, chimpanzees, gorillas and other species, and compared different aspects of the cell types.

What they found: Researchers reported their findings in 21 papers published today in several Science journals.

Diversity: They found more than 3,300 cell types in the human brain that could be grouped into 461 clusters.

  • They also identified new cell types in the brain's cerebral cortex — the region that is key to memory, language and other essential functions.
  • But they found the brain stem and hypothalamus have many more types of neurons than the cerebral cortex.
  • "We were a bit surprised ... it probably reflects how complex the brain stem is in terms of its circuitry and composition," says Kimberly Siletti, a postdoctoral researcher at the Karolinska Institute in Stockholm and co-author of the study describing the cell types.

Evolution: Other scientists compared the cell types in humans, chimpanzees and other species. They found they surprisingly share all of the same cell types.

  • "People always want to know what is special about humans. What is more interesting and important is what is conserved," says Edward Callaway, a neuroscientist at the Salk Institute for Biological Studies and a co-author of the paper.
  • But there were differences in the proportions of cell types and the researchers found a few hundred genes that were active in humans and not in chimpanzees. The expression of those genes seems to be involved in the wiring of the neurons, suggesting that is a key difference between humans and chimpanzees.

Between the lines: Mice are often used to study human diseases but they can be limited for modeling neurologic diseases.

  • The comparisons between the mouse and human brain in the new research suggest "what we found previously in simple experimental organisms, like the mouse, actually applies to the human brain," says Joseph Ecker, a molecular biologist at the Salk Institute and co-author of one of the studies. "But of course, there's more complexity."
  • "We're not going to ever be able to study the human brain at the resolution we can in a mouse," Callaway says. Studies of the brain are invasive, expensive and raise ethical issues. "And we can do a lot of things in monkeys that we can't do in humans but can in mice. So we need all of these levels."

What they're saying: "It is essential to have a comprehensive atlas of the human brain," Sergiu Pasca, a neurobiologist at Stanford University who wasn't involved in the new research, tells Axios in an email.

  • To understand the genes associated with neuropsychiatric disorder, "we need to know — as a first step — in what cells in the brain and when they are expressed," he adds.

The big picture: The census is part of a broader effort from the National Institutes of Health's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to map the brain of humans, monkeys, mice and other species.

  • The EU's Human Brain Project, which ended last month, had a goal of modeling the entire brain in a computer.

What to watch: Researchers still need to determine what the different cell types do, where exactly they are found in the brain and how they connect to form circuits.

  • These studies focused on gene expression but much of what a cell does is determined by the proteins that genes encode. "RNA won’t tell us everything," Siletti says.
  • There's "a lot of work to do in putting the full picture together," she says.
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