Brain atlas: Scientists create an unprecedented map of the human brain

Scientists have created an atlas of the human brain revealing features that distinguish us as humans and offer insight into certain diseases. The package of 21 studies is a collective effort characterised of more than 3,000 human brain cell types that may provide an insight into the diversity of brain cells and why some cells are more susceptible to mutation.

The researchers also revealed chimpanzee neurons are more like gorilla neurons, despite chimpanzees being closely related to humans but it is hoped the study will help answer “fundamental scientific questions about the human brain”. The core work to create the map was found in three studies.

A team led by Wei Tian, of The Salk Institute For Biological Studies in California, mapped epigenomes – the chemical compound that tells genomes what to do – in the brain by probing DNA methylation and chromatin in 517,000 cells from 46 regions of three male brains. In total, 188 cell types and characterised their molecular signatures – sets of genes, proteins, genetic variants or other variables that can be used as markers were found. From this, the team created “a single-cell DNA methylation and 3D genome structure atlas” of the human brain which they said will be a “valuable resource” to fuel further research into brain cell diversity, gene regulation mechanisms and new genetic tools.

Another study, led by Kimbeley Siletti of the Karolinska Institutet in the Netherlands, claimed the human brain has not been “comprehensively surveyed”, with “few regions outside the cerebral cortex” profiled. To overcome this, the team used RNA sequencing to profile cells sampled from throughout the entire human brain and post-mortem tissue was taken from three donors from 100 locations across the forebrain, midbrain and hindbrain.

The data collected comprised more than three million cells and two million neurons where researchers clustered these and found the neurons “varied extensively” across the different regions. Glia – cells which support, connect and protect the neurons in the nervous system – were also found to vary and the brainstem was also found to have an “extremely diverse set of neurons that may support innate behaviours”.

The findings suggest each area of the brain contains specific cell types and states, researchers said, which could provide a basis for exploring diseases that exhibit regional variation, including cancer and neurodegenerative disease.

Another study led by Yang Eric Li, of Washington University in St Louis, looked at the brain’s accessibility to chromatin – a mix of DNA and proteins that form chromosomes found in cells – to better understand mental illness. Using three neurotypical adult volunteers, the team used 1.1 million cells from 42 distinct brain regions.

They said the atlas offered insights into gene-regulatory programmes that shape the diversity of brain cells and “promises to advance our understanding of brain function and neuropathology, ultimately offering avenues for more effective approaches to addressing neuropsychiatric disorders”.

The findings have been published in the journals Science, Science Advances and Science Translational Medicine. They form part of the National Institutes of Health’s BRAIN Initiative Cell Census Network (BICCN), which launched in 2017. Writing in Science, senior editor Mattia Maroso said the data collected by BICCN will “allow researchers to tackle fundamental scientific questions about the human brain”.

Elsewhere, a study led by Nikolas Jorstad compared single nucleus transcriptomics in adult humans, chimpanzees, gorillas, rhesus macaques and common marmosets. They found chimpanzee neurons are more like gorilla neurons than human neurons.

Mr Maroso added: “These techniques have traditionally been mostly used in preclinical studies involving rodents and other experimental models. The work presented here showcases how human research might have now caught up with preclinical work.”