Researchers have compiled an atlas of cell types in the human brain
Neurobiologists have classified nerve cells in the human brain that differ in gene activity and function. The results of the study are published in a special issue of the journal Science.An international team of scientists led by the Salk Institute for Biological Studies has compiled an atlas describing the different subtypes of human brain cells. The neuroscientists analyzed more than half a million brain cells from three people to describe the 188 cell types with different active genes that make up the human brain in unprecedented detail.
Every cell in the body contains the same DNA sequence, but different genes are "read," translated into RNA, and used to make proteins in different types. The diversity of proteins provides the functional differences between cells and the complexity of the brain.
The human brain study is based on a method that researchers at the Salk Institute have previously used to identify brain cell subtypes in mice. In 2020, scientists profiled 161 cell types in the mouse brain based on methyl chemical markers along the DNA. These markers determine when certain genes are turned on or off.
In the new study, scientists used the same tools to determine DNA methylation patterns in more than 500,000 brain cells from 46 brain regions of three healthy adult men. While mouse brains are virtually identical across animals and contain about 80 million neurons, human brains vary much more and contain about 80 billion neurons.
To improve the accuracy of the results, the researchers also used a second method that analyzed the three-dimensional structure of the DNA molecules in each cell to gain additional information about which gene sequences are actively used. Areas of DNA that are exposed are more likely to be accessible to cells than tightly coiled stretches of DNA.
The combined analysis allowed the identification and characterization of 188 different subtypes of human brain cells. Knowing how different cell types function from which DNA sequences is crucial not only to understanding how the brain works, but also to understanding how mutations in DNA can cause brain disorders and, consequently, how to treat these disorders.
The study is part of a large-scale BRAIN initiative to characterize the full array of cells in the mammalian brain. The special issue of the journal Science features 21 studies by scientists using a variety of methods to describe the diversity of brain cells in the adult and developing brains of humans and other primates.