What differentiates the human brain from that of all other animals, including even our closest primate relatives? In an analysis of cell types in the prefrontal cortex of four primate species, Yale researchers identified species-specific features, particularly in humans, they report Aug. 25 in the journal Science.
And they discovered that what makes us human can also make us susceptible to neuropsychiatric illnesses.
For the study, the researchers looked specifically at the dorsolateral prefrontal cortex (dlPFC), a region of the brain that is unique to primates and essential for higher-order cognition. Using a single-cell RNA sequencing technique, they profiled gene expression levels in hundreds of thousands of cells taken from the dlPFC of adult humans, chimpanzees, macaques and marmoset monkeys. .
“Today, we consider the dorsolateral prefrontal cortex to be central to human identity, but we still don’t know what makes it unique in humans and sets us apart from other primate species.” said Nenad Sestan, Harvey Professor of Neuroscience and Kate Cushing at Yale, Professor of Comparative Medicine, Genetics. and psychiatry, and the main senior author of the article. “Now we have more clues.”
To answer this, the researchers first asked if there were cell types only found in humans or other non-human primate species being analyzed. After pooling cells with similar expression profiles, they revealed 109 shared primate cell types, but also five that were not common across all species. These included a type of microglia, or brain-specific immune cell, that was only present in humans and a second type shared only by humans and chimpanzees.
The type of microglia specific to humans exists throughout development and adulthood, the researchers found, suggesting that the cells play a role in maintaining brain maintenance rather than fighting against the brain. sickness.
“We humans live in a very different environment with a unique way of life compared to other primate species; and glial cells, including microglia, are very sensitive to these differences,” Sestan said. “The type of microglia found in the human brain may represent an immune response to the environment.”
An analysis of gene expression in microglia revealed another human-specific surprise: the presence of the FOXP2 gene. This finding has sparked great interest because variants of FOXP2 have been linked to dyspraxia verbalis, a condition in which patients have difficulty producing language or speech. Other studies have also shown that FOXP2 is associated with other neuropsychiatric diseases, such as autism, schizophrenia and epilepsy.
Sestan and colleagues found that this gene exhibits primate-specific expression in a subset of excitatory neurons and human-specific expression in microglia.
“FOXP2 has intrigued many scientists for decades, but we still had no idea what makes it unique in humans compared to other primate species,” said Shaojie Ma, postdoctoral associate at Sestan’s lab and lead co-author. We are extremely excited about the findings of FOXP2 as they open up new directions in the study of language and disease.”
The research was funded by the National Institutes of Health and the National Institute of Mental Health.
Other authors include co-lead author Mario Skarica, research associate in neuroscience at Yale School of Medicine; senior co-author Andre Sousa, assistant professor of neuroscience at the University of Wisconsin-Madison; and co-lead author Stephen M. Strittmatter, Vincent Coates Professor of Neurology and Yale Professor of Neuroscience, Chair of the Department of Neuroscience and Director of the Kavli Institute for Neuroscience.