Imagine a massive traffic jam clogging a busy highway. Horns blare, motorcycles weave through stalled cars—but only when you zoom in do the real culprits emerge: cyclists stubbornly riding against traffic.
In the same way, pinpointing the precise culprits behind harmful biological processes—such as excessive scarring (fibrosis) in organs like the kidneys and lungs—has long remained challenging even though this affects almost a billion people worldwide. But thanks to the emergence of single-cell isolation technologies, researchers have been able to zero in on the specific immune cells causing trouble.
In a comprehensive review published in Nature Reviews Immunology , a Duke-NUS-led team compiled a 'handbook' of key insights from over 200 studies on immune cell types, their location and their behavioural changes over time, providing an evidence-based start line to accelerate scarring research. Their start line points to the changeable behaviour of a type of immune cell, called macrophage, that has emerged as a key driver of excessive scarring.
“Think of macrophages as having 'happy’ faces, promoting healthy tissue repair, or ‘angry’ faces, causing harmful scarring. Recent technological advances have made it possible to identify exactly which cells trigger fibrosis, opening new doors for targeted treatments,” said Associate Professor Jacques Behmoaras from Duke-NUS’ Cardiovascular and Metabolic Disorders Programme, the corresponding author of the review paper.
But what are these instigators of fibrosis like? How do they function and interact with the environment around them? And is there any way to prevent them from harming the body? Since the first study involving single-cell transcriptomics [1] was published in 2009, scientists have come closer than before to fully answering these questions by observing macrophages from a spatial and temporal perspective. In their summary of these findings, Assoc Prof Behmoaras and his team highlight the following crucial discoveries:
In fibrosis, SPP1+ macrophages, which promote scarring, increase in number and signal fibroblasts to produce scar tissue components in excess, disrupting a once-balanced relationship.
Systems geneticist and co-author Professor Enrico Petretto , Director of Duke-NUS’ Centre for Computational Biology , said of the potential of his team’s work: “As we continue making significant progress in fibrosis research, we wanted to create a clear and accessible resource – a 'handbook'—to guide translational researchers globally. Our aim is to accelerate discoveries, foster new ideas and ultimately transform treatment for millions affected by fibrosis.”
With this ‘handbook’ in hand, Duke-NUS researchers hope to turn today's scientific insights into tomorrow's life-changing therapies, bringing fresh hope to millions worldwide battling fibrosis.
[1] Tang, F., Barbacioru, C., Wang, Y., Nordman, E., Lee, C., Xu, N., Wang, X., Bodeau, J., Tuch, B. B., Siddiqui, A., Lao, K., & Surani, M. A. (2009). MRNA-seq whole-transcriptome analysis of a single cell. Nature Methods, 6(5), 377–382. https://doi.org/10.1038/nmeth.1315
Nature Reviews Immunology
Systematic review
Cells
The spatial and temporal activation of macrophages during fibrosis
4-Jun-2025
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