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What distinguishes the human brain from that of all other animals — including even our closest primate relatives? Yale researchers identified species-specific — particularly human-specific — features in an analysis of cell types in the prefrontal cortex of four primate species. They reported their findings on August 25, 2022, in the journal Science.

What they found that makes us human may also make us susceptible to neuropsychiatric diseases.

For the study, the scientists looked specifically at the dorsolateral prefrontal cortex (dlPFC). This is a brain region that is unique to primates and essential for higher-order cognition. Using a single-cell RNA-sequencing technique, the researchers profiled expression levels of genes in hundreds of thousands of cells collected from the dlPFC of adult humans, chimpanzees, macaque, and marmoset monkeys.

“Today, we view the dorsolateral prefrontal cortex as the core component of human identity, but still we don’t know what makes this unique in humans and distinguishes us from other primate species,” said Nenad Sestan. He is the lead senior author of the paper, the Harvey and Kate Cushing Professor of Neuroscience at Yale, professor of comparative medicine, of genetics, and of psychiatry.  “Now we have more clues.”

To answer this, the scientists first asked whether there are there any cell types uniquely present in humans or other analyzed non-human primate species. After grouping cells with similar expression profiles, they revealed 109 shared primate cell types. They also discovered five that were not common to all species. These included a type of microglia, or brain-specific immune cell, that was present only in humans and a second type shared by only humans and chimpanzees.

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Yale researchers have identified human-specific features in the prefrontal cortex.

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