Do you know? 3,000 Types Of Cells In The Human Brain

 Human Brain

A new look at the human brain is beginning to reveal the inner life of its cellular inhabitants.

The human brain contains an amazing collection of diverse cells, and no two brains are cellularly alike. These are the prevailing findings of 21 papers published online on October 12 in Science, Science Advances and Science Translational Medicine.

The results begin to scratch the surface of understanding the mysteries of the brain. Nevertheless, they provide the most intimate look yet at the cells that make up the brain, and clues about how the brain enables thoughts, actions and memories. The collection of data can also guide researchers in discovering the causes of brain disorders such as schizophrenia, Alzheimer's disease and depression.

The new brain map

The new brain map is the result of a coordinated international research effort called the National Institutes of Health's Brain Initiative Cell Census Network, or BICCN, which grew rapidly in 2017. Many of the studies in the collection are based on a powerful technique called single-. Cell Genomics. The method reveals which genes are active inside a single cell, information that provides clues about the cell's identity and function.

BICCN, researchers

As part of the BICCN, researchers examined all types of brains. One project details the cells in small pieces of living brain tissue taken from 75 people undergoing surgery for tumours or epilepsy, an approach that has been used on a smaller scale before (SN: 8/7/19). Another looked at samples taken from the brains of 17 dead children. Yet another looked at brain tissue from seven people, seven chimpanzees, four gorillas, three rhesus macaques and three marmosets.

The resolution provided by single-cell genomics 

The resolution provided by single-cell genomics revealed details about human brain cells in a way that previous methods could not. "It's remarkable how well it works," says Ed Lein, a neuroscientist at the Allen Institute for Brain Science in Seattle and one of the lead researchers in the BICCN group. Collectively, the new studies describe more than 3,000 cell types that reside in the human brain.

Lain says the main finding is that "the brain is really complex from a cellular standpoint."

Amid that complexity, several important insights have already emerged, including clues to how human brains develop, how they vary between people, and how they differ from the brains of close primate relatives.

Growing Brain

Some studies focused on very young brains. For example, a study of the first two trimesters of brain development revealed previously unknown details about the identity of nerve cells in the thalamus, a type of pathway for information coming into the brain. Many of those cells, called GABAergic neurons, originate elsewhere in the developing brain and migrate to the thalamus.

Other results show that the early years matter a lot. Neuroscientist Seth Ament of the University of Maryland School of Medicine in Baltimore and his colleagues looked at brain cells in the cerebellum, a brain region in the posterior part of the brain. Children who died due to swelling in the brain, They had altered levels of genes active in certain types of nerve cells – Purkinje and Golgi neurons. The pattern, which is based on eight brains, suggests that inflammation early in life may alter nerve cell development in certain locations.

"I'm surprised we saw something so consistent across the samples," Ament says.

Unique Mind

Some studies focused on variability between brain regions and people.

One study looked at cells from about 100 spots taken from the brains of four adults. The researchers found, among many other things, that cells called astrocytes use their genes differently depending on where they live. The finding indicates that these cells, which are known to help nerve cells make connections and keep brain tissue healthy, may be specific to their region.

Another study examined eight areas of the neocortex, the wrinkled outer region responsible for sophisticated thinking. The scientists found that the cells in those areas are somewhat standardized, sorted into 24 consistent categories. However, the proportion of cells varies between regions. What this means for how these fields work is anyone's guess.

Similarities also exist between people. When researchers compared brain cells from 75 people they found highly consistent patterns of cells. But there was a lot of scope there too. For example, microglia, immune cells in the brain that also form nerve cell connections, were particularly unique in the genes they use from one person to another.

Primate Brain

Some research compares the human brain to that of primate relatives, including chimpanzees, gorillas, rhesus macaques, and marmosets. By looking at cells in the brains of other primates, Lain says, "Ultimately we have to ask the question of what makes humans unique."

Overall, the cells of the middle temporal gyrus, a part of the brain's cortex, did not differ much between primate brains. "It's really remarkable that this complex cellular makeup is so preserved," says Lein. "But you have these changes inside you too."

The researchers found that compared to other primates, human brain cells use certain genes differently – specifically, genes related to how cells make connections and communicate. The analysis also revealed a few hundred genes that appear to behave in human-specific ways in brain cells. Researchers don't yet know what those genes might be doing.

Imaging neuroanatomist Matthew Glasser

Imaging neuroanatomist Matthew Glasser cautions that it may be difficult to tell which brain areas are comparable between primates. Still, the results are "the first step in doing something really cool," says Glasser, of Washington University School of Medicine in St. Louis, who was not involved in these studies

Even better mind maps are coming

Overall, the progress shown by these and related results "is truly mind-blowing," says cortical cartographer David Van Essen, who did not work on the new studies. “The community will certainly benefit from what is revealed in this collection of letters.”

But, more importantly, this is just a glimpse of what is to come. "I don't think this is the endpoint," says Van Essen, also of the University of Washington. "It's more midpoint."

Ament agrees. “These papers, as important as I think they are, are not the end,” he says. “This is just the beginning and we have a lot more work to do.”

Lein says the new brain maps will likely be revised, refined, and added to. Scientists are already working on the next iterations, which seek to combine zoomed-out views of brain networks and brain behaviour with the microscopic details provided by single-cell technology.

"Now that we have these techniques," Glasser says, "we're trying to combine them with brain imaging and systems neuroscience to really figure out the puzzle.