Several research teams worked together to create the most comprehensive cellular atlas of the human brain to date and, among other things, identified more than 3,000 types of brain cells. For example, they examined how nerve cells in the brain differ from each other in their functions. A total of 21 studies, which are part of the NIH’s “Brain Initiative”, are presented in the journals “Science”, “Science Advances” and “Science Translational Medicine”.
A team led by Kimberly Siletti of the Karolinska Institute in Stockholm examined tissue from 14 human brains. Using a new method, it clarified which RNA sequences were present in individual brain cells. RNA (ribonucleic acid) serves, among other things, as a transmitter of information from genetic material for the production of proteins. Depending on the tasks of the cells, the RNA sequences in them differ, from which the researchers managed to derive 3,313 different types of cells. The dataset for this work included more than three million brain cells.
In two additional studies, a team led by Yang Li of the University of California and another led by Wei Tian of the Salk Institute for Biological Studies examined the epigenetics of individual brain cells. Epigenetic mechanisms determine how often which gene is recovered from a cell’s genome. Epigenetics is also influenced by the environment, diet and aging. Taken together, these three studies created a brain cell atlas that characterizes individual types of brain cells and assigns them to individual regions. This atlas is freely accessible to all scientists.
Beginning of a new era
“This is truly the beginning of a new era in brain research, in which we can better understand how brains develop, age and are affected by disease,” said Joseph Ecker of the Salk Institute, who is involved in several of the studies.
The activities for the brain cell atlas are grouped in the BICCN (Brain Initiative Cell Census Network) project. BICCN now also makes it possible to obtain more information about the human brain, for example how the brains of humans and monkeys differ. That’s what a team led by Nikolas Jorstad, from the Allen Institute for Brain Science in Seattle, did, among others: they examined samples from a region of the brain associated with facial recognition and reading in humans, adults, chimpanzees, gorillas, monkeys rhesus and marmosets.
“Only a few hundred genes showed human-specific patterns, suggesting that relatively few cellular and molecular changes clearly define the structure of the adult human cerebral cortex,” Jorstad and colleagues summarize their findings.
But researchers are also concerned about advances in human medicine: “Mapping the different cell types in the brain and understanding how they work together will ultimately help us discover new therapies that target individual cell types that are relevant for specific diseases,” says Bing Ren. from the University of California. Ren is the senior author of the study by Li and colleagues. Scientists have been able to link molecular biological aspects of 107 different brain cell subtypes to a wide range of neuropsychiatric illnesses, including schizophrenia, bipolar disorder, Alzheimer’s disease and severe depression.
Other research concerned the development of the human brain from the early embryonic stage. This research also gave Sten Linnarsson’s team at the Karolinska Institute in Sweden new insights into glioblastoma, one of the most aggressive brain tumors. Tumor cells are similar to immature stem cells that try to form a brain, but in a completely disorganized way. “We observed that these cancer cells activated hundreds of genes specific to them, and it could be interesting to investigate whether there is potential to find new therapeutic targets,” explained Linnarsson.