Midbrain dopaminergic neurons below a microscope. Credit score: Hilary Toh, Duke-NUS Medical Faculty
Scientists from Duke-NUS Medical Faculty and their collaborators have created one of the complete single cell maps of the growing human mind. The atlas captures almost each cell sort, their genetic fingerprints, and the way they develop and work together. It additionally benchmarks best-in-class laboratory strategies for producing high-quality neurons, marking a significant step towards new therapies for Parkinson’s illness and different mind problems.
The work is printed within the journal Science Advances.
Parkinson’s illness is Singapore’s second commonest neurodegenerative dysfunction, affecting about three in each 1,000 individuals aged 50 and above. The situation damages midbrain dopaminergic neurons—cells that launch the chemical dopamine to regulate motion and studying. Restoring these cells might at some point assist alleviate signs similar to tremors and mobility loss.
To higher perceive how these neurons develop when grown in a laboratory, the Duke-NUS group constructed a two-step mapping framework referred to as BrainSTEM (Mind Single-cell Two tiEr Mapping). Working with companions, together with the College of Sydney, they analyzed almost 680,000 cells from the fetal mind to map the complete mobile panorama.
The second higher-resolution projection focuses on the midbrain—pinpointing dopaminergic neurons with higher precision. This “comprehensive reference map” now supplies scientists worldwide with a typical to judge the accuracy of midbrain fashions, in comparison with the actual human mind.
Dr. Hilary Toh, an MD-Ph.D. candidate from the Neuroscience & Behavioral Issues program at Duke-NUS Medical Faculty and one of many first authors of the paper, stated, “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 minimizing side effects, paving the way to offer alternative therapies to people living with Parkinson’s disease.”
The examine discovered that many strategies used to develop midbrain cells additionally produced undesirable cells from different mind areas. This reveals that each the lab strategies and the information evaluation want enchancment to detect and take away these off-target cells.
A BrainSTEM map of the completely different cell sorts within the midbrain. Credit score: Xu Lisheng, Duke-NUS Medical Faculty
Dr. John Ouyang, Principal Analysis Scientist from Duke-NUS’ Middle for Computational Biology and a senior writer of the examine, stated, “By mapping the brain at single-cell resolution, BrainSTEM gives us the precision to distinguish even subtle off-target cell populations. This rich cellular detail provides a critical foundation for AI-driven models that will transform how we group patients and design targeted therapies for neurodegenerative diseases.”
Assistant Professor Alfred Solar from Duke-NUS’ Neuroscience & Behavioral Issues program, who’s additionally a senior writer of the paper, added, “BrainSTEM marks a significant step forward in brain modeling. By delivering a rigorous, data-driven approach, it will speed the development of reliable cell therapies for Parkinson’s disease. We’re setting a new standard to ensure the next generation of Parkinson’s models truly reflects human biology.”
The group will present their mind atlases as an open-source reference and the multi-tier mapping course of as a ready-to-use package deal. With BrainSTEM being a framework that may be utilized to sieve out any cell sort within the mind, labs worldwide can deploy it to deepen insights, refine workflows and speed up discovery throughout neuroscience.
Professor Patrick Tan, Senior Vice-Dean for Analysis at Duke-NUS, stated, “This study redefines the benchmark—establishing multi-tier mapping as essential for capturing cellular detail in complex biological systems. By revealing how the human midbrain develops in such detail, we will accelerate Parkinson’s research and cell therapy, delivering better care and offer hope to people living with the disease.”
Extra data:
Hilary S. Y. Toh et al, BrainSTEM: A single-cell multiresolution fetal mind atlas reveals transcriptomic constancy of human midbrain cultures, Science Advances (2025). DOI: 10.1126/sciadv.adu7944
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