Multiple Nature papers: Neuroscientists complete the first comprehensive brain cell atlas

A large number of new studies have shown that the area of ​​the brain responsible for initiating this action-the primary motor cortex that controls the action-has as many as 116 different types of cells that work together to make this action happen
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On October 6th Nature magazine published 17 related studies.
These works consist of a huge research consortium.
This is the first step of a long-term project that aims to generate an atlas of the entire brain to help understand the nerves in our brains.
How the network controls our body and mind, and how they are destroyed when there are psychological and physical problems
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Helen Bettap, a cellular neuroscientist at the University of California, Berkeley, asked: "If you think of the brain as an extremely complex machine, how can we understand it without first breaking it down and knowing its parts? ? The first page of any manual on how the brain works should read: Here are all the cellular components, this is their number, this is where they are located, and who they are connected to
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Previously, individual researchers have identified dozens of cell types based on the cell's shape, size, electrical properties, and the genes expressed in them
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The new research has discovered five times more cell types, although many are subtypes of known cell types

Although the current paper only deals with the motor cortex, the BRAIN Initiative Cell Census Network (BICCN)-created in 2017-attempts to map all the different cell types of the entire brain, including more than 160 billion individual cells, including neurons and called Support cells for glial cells
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The "Brain Project" was initiated by then-U.

Betip said: "Once we define all these parts, we can further understand how these parts work together, how they form a functional circuit, how to ultimately produce perception and behavior, and more complex things
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Betip and colleague Dirk Hawkmeyer of the University of California at Berkeley have used CRISPR-Cas9 technology to label a specific cell type with fluorescent markers in mice, allowing them to track the number of these cells throughout the brain.
Connect
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She said that in this flagship journal paper, the Berkeley team created two "knock-in" report mice, providing novel tools for elucidating the connections between newly identified cell types

"One of the many limitations we face in developing effective treatments for human brain diseases is that we know little about which cells and connections are affected by specific diseases, so we cannot precisely determine the target and location we need to target
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About the composition The detailed information on the cell types and characteristics of the brain will ultimately help develop new therapies for neurological and neuropsychiatric diseases

Other researchers collaborated in an earlier study to analyze all the active genes in a single dopamine-producing cell in the midbrain of mice
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The structure of the mouse midbrain is similar to that of the human brain

The scRNA-seq technology is one of nearly 12 different experimental methods used by the BICCN team to describe different cell types in three different mammals: mice, marmosets, and humans
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Four of these methods involve different methods of identifying gene expression levels, determining the chromatin structure of the genome, and DNA methylation status, which are called epigenomes

"This is the most comprehensive description of these cell types, with high resolution and different methods.
The conclusion of this paper is that there is significant overlap and consistency in determining cell types using these different methods
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A group of statisticians combined the data of all these experimental methods to determine how to best classify or aggregate cells into different types, and infer the differences based on the differences in expression and epigenetic characteristics observed between these cells Function
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Sandrine Dudoit, professor and director of statistics at the University of California, Berkeley, said that although there are many statistical algorithms to analyze this type of data and identify clusters, the challenge is to determine which clusters are truly different from other clusters—really different cell types
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She and Elizabeth Purdom, a biostatistician and associate professor of statistics at the University of California, Berkeley, are key members of the statistics team and co-authors of this flagship paper
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Dudoit said: "The idea is not to create another new clustering method, but to find ways to use the advantages of different methods and combinations of methods, and evaluate the stability of the results and the repeatability of the clusters you get
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"This is a key message for all these studies looking for new cell types or new cell types: no matter what algorithm you try, you will get clusters, so confidence in your results is the key
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Bateup pointed out that the number of individual cell types found in this new study depends on the technology used, ranging from tens to 116
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For example, a study found that in this area of ​​the brain, the number of different types of inhibitory neurons in humans is about twice that of excitatory neurons, while the number in mice is five times that of excitatory neurons
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"Before, we had 10 or 20 different cell types, defined, but we don’t know whether cells are defined by their gene expression patterns.
Those definitions are based on electrophysiological properties, or the same neuron type is defined for them.
The form," Bateup said
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Hockemeyer said: "The major development of BICCN is that we have combined many different methods of defining cell types and integrated them to propose a consensus classification method that is not only based on gene expression, physiology or morphology, And all these characteristics are considered
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" "So, now we can say that this particular cell type expresses these genes, has this shape, has these physiological characteristics, and is located in this particular area of ​​the cerebral cortex
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So, you are right about this.
There is a deeper and more fine-grained understanding of these cell types and their basic properties
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DuDoit warned that future research may show that the number of cell types identified in the motor cortex is overestimated, but the current research is a good start for assembling the entire brain cell map
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She said: "Even among biologists, there is also a very Big disagreements
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” “Nevertheless, these results show the power of collaboration and joint efforts of different groups
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We started with a biological problem, but biologists alone cannot solve this problem
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To solve such a challenge is challenging.
For the big problem of sex, you need a team of experts from different disciplines who can communicate and cooperate well
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Journal Reference :

1. BRAIN Initiative Cell Census Network (BICCN).
   A multimodal cell census and atlas of the mammalian primary motor cortex .
   Nature , 2021; 598 (7879): 86 DOI: 10.
   1038/s41586-021-03950-0