How gene activity changes in human brain cells from pre-birth to adulthood has been illustrated in a new map developed by Australian scientists, helping to pinpoint cell states in diseases like brain cancer or certain mental illnesses.
The function of diverse cells in the brain has been mapped in a “world-first” by a team at the Harry Perkins Institute of Medical Research and The University of Western Australia.
Professor Ryan Lister, known for his work generating the first comprehensive maps of the human epigenome, led the research, which was published in the peer-reviewed Cell journal this week.
“Our new study now focuses on how gene activity and its controlling factors change as we mature,” Professor Lister said.
“Our previous research assembled maps of how the epigenome changes during human brain development.”
By age 30, the human brain is still maturing and the diversity of the many billions of cells that make up the organ keep building. Lister explained that every cell had its own specialised function, meaning that over time, people’s cognitive abilities also grow and advance.
“Think of the enormous differences in what an adult can do compared to a child, toddler, or newborn,” Lister said.
“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.”
Lister’s pioneering work in epigenomics — the study of the molecular code that controls gene activity — led to the most comprehensive maps of the human epigenome in the world. His other research into plant and animal systems has shed “ground-breaking” light on our understanding of genome regulation, stem cell biology, and brain development.
Finally out in @CellCellPress! Our map of human prefrontal cortex maturation (ga24-40yrs) across all brain cell types. 🧵 https://t.co/NF8xI0loQm
— Saskia Freytag (@SaskiaFreytag) October 31, 2022
The high-resolution map will serve as a tool to accurately identify altered states of brain-cell development in neurological and psychiatric disorders. This includes mental illnesses such as schizophrenia, or brain cancer, in which cell states are aberrant.
To develop the database, researchers examined brain tissue from post-mortem neurotypical individuals.
One of the paper’s co-authors, Dr Rebecca Simmons, said researchers had previously lacked knowledge about gene activity in the brain and the influence of different factors that may control it from birth to death.
“We … used new technologies for mapping gene activity at single-cell resolution to track each individual type of cell as we develop and age,” Simmons said.
Dr Chuck Herring, who also contributed to the study, said the map specifically identified how each different type of brain cell in the prefrontal cortex changed as people aged.
“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.
“From mid-gestation through to adulthood in normal individuals, [it] predicts the cellular factors that control these changes,” he said.
According to Dr Daniel Poppe, another co-author, because most disorders affecting the brain progress over time, the map may help clinicians find pick-up problems before the diseases advance.
“This would enable earlier intervention in the future,” Poppe said.
“It will be a great resource for neurologists, neuroscientists, and those working in developmental biology.”
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