Mapping gene activity in brain cells from pre-birth to adulthood

Researchers from the Harry Perkins Institute of Medical Research and The University of Western Australia say they have created a world-first map of the gene activity changes that occur in the diverse cells of the brain from before birth through to adulthood, filling a major gap in our knowledge of gene activity and the factors controlling it in the brain.

By having this map of normal brain cell development, researchers will now be able to identify altered states more accurately in neurological and psychiatric disorders such as schizophrenia, or aberrant cell states in diseases such as brain cancer. The research has been published in the journal Cell.

“Different neurological and psychiatric diseases emerge at specific times during development, such as autism spectrum disorders in the early years or neuropsychiatric disorders such as schizophrenia emerging in the teens sometimes, so there are common time periods during development where certain disorders emerge and they will have a cellular basis,” said study co-author Dr Saskia Freytag.

Co-author Dr Chuck Herring added, “This high-resolution map shows how the gene activity of each different type of brain cell in the prefrontal cortex changes as we mature, from mid-gestation through to adulthood in normal individuals, and predicts the cellular factors that control these changes.

“Without a map of normal development, we don’t have a reference to identify what is abnormal, and how it might contribute to brain disorders.”

Our brains contain many billions of cells and a huge diversity of different cell types, each with their own specialised functions. But this takes a long time to build, with brain maturation continuing into the third decade of life.

“Through this long process our cognitive abilities emerge, grow, change and advance; think of the enormous differences in what an adult can do, compared to a child, toddler or newborn,” said study leader Professor Ryan Lister, who previously generated the first comprehensive maps of the human epigenome.

“Underpinning these advances are complex changes in the cells of our brain, as they migrate, grow, form and refine connections, and communicate. Importantly, these changes require the correct control and timing of gene activity, and our new work provides the first reference map of this.”

Co-author Dr Rebecca Simmons explained that the researchers obtained post-mortem brain tissue from neurotypical individuals and used new technologies for mapping gene activity at single cell resolution to track each individual type of cell as we develop and age. As well as helping scientists to better understand brain disorders, Lister said the maps can be used to develop improved models of brain cells for modelling diseases and new drug discovery.

“It will be a great resource for neurologists, neuroscientists and those working in developmental biology,” added co-author Dr Daniel Pope. “Most disorders affecting the brain progress over time, so these findings could allow researchers to identify initial events before these diseases manifest. This would enable earlier intervention in the future.”

Image credit: iStock.com/deliormanli

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