Healthcare (Commonwealth Union) – Scientists from the Duke-NUS Medical School in Singapore, together with international collaborators, have developed one of the most detailed single-cell atlases of the developing human brain to date. This map charts nearly every cell type, their genetic signatures, and how they form and communicate. It also sets a new benchmark for laboratory techniques that generate high-quality neurons—an important advance toward future treatments for Parkinson’s disease and other neurological conditions.
The increasing aging population across the world can result in an increase in parkinson’s disease rates, affecting roughly three in every 1,000 individuals aged 50 and above. The disorder results from damage to midbrain dopaminergic neurons, which produce dopamine—a chemical essential for movement and learning. Replacing or regenerating these neurons could one day ease symptoms such as tremors and difficulty moving.
To shed light on how these neurons develop in lab conditions, the Duke-NUS team created a two-tiered mapping framework known as BrainSTEM (Brain Single-cell Two tiEr Mapping). Partnering with institutions including the University of Sydney, they examined nearly 680,000 fetal brain cells to chart the full cellular landscape.
The second, higher-resolution layer of the map zeroes in on the midbrain, identifying dopaminergic neurons with remarkable precision. This comprehensive reference atlas now offers researchers worldwide a gold standard for testing how faithfully lab-grown midbrain models replicate the real human brain.
Dr Hilary Toh, an MD-PhD candidate from the Neuroscience & Behavioural Disorders programme at Duke-NUS Medical School who is one of the first authors of the paper, says “Our data-driven blueprint helps scientists produce high-yield midbrain dopaminergic neurons that faithfully reflect human biology. Grafts of this quality are pivotal to increasing cell therapy efficacy and minimising side effects, paving the way to offer alternative therapies to people living with Parkinson’s disease.”
The research, recently published in Science Advances, revealed that several techniques used to cultivate midbrain cells also generated unintended cells originating from other parts of the brain. This highlights the need to refine both laboratory procedures and data analysis methods to better identify and eliminate these off-target cells.
Dr John Ouyang, Principal Research Scientist at Duke-NUS’ Centre for Computational Biology and senior author of the paper, indicated that by charting the brain at single-cell resolution, BrainSTEM enables them to detect even the most subtle off-target cell groups with precision. Dr Ouyang further indicated that this detailed cellular information lays the groundwork for AI-powered models that could revolutionise how they classify patients and develop targeted treatments for neurodegenerative disorders.
Assistant Professor Alfred Sun from Duke-NUS’ Neuroscience & Behavioural Disorders Programme, and a senior author of the study, indicated that BrainSTEM represents a major leap in brain modelling and despite the fact that it is robust, data-driven design, it will help accelerate the creation of dependable cell therapies for Parkinson’s disease. He further indicated that they are raising the bar to make sure future Parkinson’s models accurately capture human biology.
The researchers plan to make their brain atlases publicly available as an open-source reference, along with the multi-layered mapping process as a ready-to-use toolkit. Since BrainSTEM can be adapted to identify any brain cell type, laboratories around the world can use it to enhance understanding, streamline methods, and drive faster breakthroughs in neuroscience.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, indicated that this work sets a new standard, showing that multi-layered mapping is vital to fully capture the complexity of biological systems at the cellular level. Professor Tan further indicated that by uncovering the intricate process of human midbrain development, we can fast-track Parkinson’s research and cell-based therapies—bringing improved treatments and renewed hope to those affected by the disease.
