Experts at the Allen Institute for Brain Science have categorized brain cell types to produce the most detailed “parts list” of the human brain to date. The research will improve our understanding of the brain, which could transform the way that brain diseases and disorders are treated.
For the first time, an ultra-high-resolution comparison of human and mouse brain cell types has been achieved. The researchers discovered that the majority of our brain cells have a counterpart in the mouse brain. These counterparts have been maintained over approximately 75 million years of evolutionary distance.
To compare and contrast the human and mouse brains, the researchers studied genes in one region of the human brain a single cell at a time.
“Just as we can use our genes to build our family trees or find long-lost relatives with services like ancestry.com or 23andme, we’re letting the genes tell us the story of our brains and their evolution,” said study senior author Dr. Ed Lein. “And in the same way that police were able to use information in those genetic databases to track down the Golden State Killer, this new high-resolution view of our brains provides a baseline to find the cells that go wrong in disease.”
The brain cell map will help scientists to interpret decades of rodent neuroscience research to be applied to the human brain. For example, some of the findings highlight key differences between mice and people that could explain why so many psychiatric drugs developed in mouse studies do not work in humans.
“The parts list of the human brain is key. That list allows us to understand what’s different between mice and human beings and what’s similar. The ultimate impact of this understanding will be better treatments for mental illnesses,” said Dr.Joshua Gordon. “The eventual goal will be to develop the complete parts list of the entire human brain. It’s a hugely ambitious goal, but this paper shows us that it’s a doable undertaking.”
The researchers found that serotonin receptors are very different between mouse and human brain cells. In mice, these proteins are used by other kinds of neurons, which means that a drug developed to act on a serotonin receptor would not affect a mouse and a person in the same way. This discovery will shed new light on why clinical researchers have struggled to develop effective treatments for depression and other serotonin-related disorders.
The finding that the 75 human brain cell types identified in the study have a counterpart in the mouse brain supports a revelation by the 2003 Human Genome Project that humans and mice have almost the same number of genes.
“Many people would assume that the human brain is more complex than the mouse brain,” said Dr. Lein. “It’s somewhat of a surprise that at least in terms of cellular diversity, that doesn’t seem to be the case. But now that we have a way to make a true apples-to-apples comparison, we start to see many differences in how the genes are used, what the cells look like and the proportions of different cell types in the brain.”
The study is published in the journal Nature.
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