Human brain cell atlas identifies links to neuropsychiatric disorders

The links between specific types of brain cell types and some common neuropsychiatric disorders have been identified for the first time.

The study is part of a major collection of new discoveries about the brain published in Science last night.

Researchers led by University of California San Diego analysed more than 1.1 million human brain cells to produce detailed maps of gene switches in brain cell types to identify the link.

The team described how they developed artificial intelligence tools to predict the influence of individual high-risk gene variants among these cells and how they may contribute to disease.

The new work was caried out as part of the National Institute of Health’s Brain Research Through Advancing Innovative Neurotechnologies Initiative (BRAIN initiative), which was launched in 2014.

The researchers analysed the cells across 42 distinct brain regions from three human brains., identifying 107 different subtypes of brain cells. They were able to correlate aspects of their molecular biology to a wide range of neuropsychiatric illnesses, including schizophrenia, bipolar disorder, Alzheimer’s disease and major depression before using the data to create machine learning models to predict how certain sequence variations in the DNA can influence gene regulation and contribute to disease.

They say their findings offer significant insights into the human brain and its pathology.

Researcher Professor Bing Ren said: “The human brain isn’t homogenous. “It’s made up of an enormously complex network of neurons and non-neuronal cells, with each serving different functions. Mapping out the different types of cells in the brain and understanding how they work together will ultimately help us discover new therapies that can target individual cell types relevant to specific diseases.

“Scaling up our work to an even greater level of detail on a larger number of brains will bring us one step closer to understanding the biology of neuropsychiatric disorders and how it can be rehabilitated.”

Another project, reported in the same journal and undertaken in Sweden and the USA, analysed three million cell nuclei from three human donors, identifying more than 3,000 cell types.

Researcher Professor Sten Linnarsson, of the Karolinska Institutet, Sweden, said: “A lot of research has focused on the cerebral cortex, but the greatest diversity of neurons we found in the brainstem. We think that some of these cells control innate behaviours, such as pain reflexes, fear, aggression and sexuality.”

Brain Cell Census Special Issue Science 12 October 2023


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