Researchers have created a detailed liver atlas, identifying more than 600,000 individual cells from 77 patients with chronic liver disease. Using this, the study (led by the Ramachandran lab) identified a group of immune cells that may offer a promising new target for preventing liver scarring. Chronic liver disease affects over 1.5 billion people globally. Over time, chronic liver damage results in fibrosis, where scar tissue builds up and affects how well the liver works. There are currently no effective treatments that directly target this scarring. A new map of liver cellsThe research team, led by Professor Prakash Ramachandran, created a comprehensive atlas, identifying over 600,000 individual liver cells by combining multiple datasets including patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This new publicly available resource will help researchers better understand how liver disease develops and identify potential treatments.Identifying immune cells linked to liver scarringUsing this atlas, the team, composed of researchers at the University of Edinburgh, in collaboration with researchers in Europe and the US, identified two groups of immune cells called TREM2+ macrophages. While these cells can have different roles, they found that one group produces a protein called OLR1 and shows pro-inflammatory and pro-fibrotic behaviour.These OLR1-producing cells were associated with progressive fibrosis across multiple causes of chronic liver disease. Analysis of anonymised and approved MASLD patient data (from a database called SteatoSITE formed within IRR) also found that livers of MASLD patients that had higher OLR1 levels were at greatest risk of chronic liver disease progression and death. Microscopy image of liver fibrotic tissue showing two subgroups of macrophage immune cells producing either OLR1 (green) or GPNMB (orange) proteins. This study finds that OLR1 macrophages are pro-inflammatory, accumulate in chronic liver disease fibrotic tissue and predict liver disease progression. Inhibiting protein signalling reduces liver scarringWhen researchers blocked OLR1 signalling in a laboratory model of the human liver, they changed the behaviour of these immune cells and reduced scarring.This suggests that targeting OLR1 could help limit liver scarring while preserving the beneficial roles of other immune cells, including those involved in tissue repair. Importantly, OLR1-blocking treatments have already been tested in people with cardiovascular disease, with no safety concerns reported in those studies. Repurposing these OLR1-targeted treatments for use as an antifibrotic in chronic liver disease could offer a more rapid route to clinical translation. Prakash Ramachandran IRR Group Leader and paper’s corresponding author The findings may also have implications for other diseases involving tissue scarring. Beyond macrophages, the new liver cell atlas also reveals numerous other cell types associated with chronic liver disease, which can be used in future research looking into disease progression and help researchers develop more targeted treatments. This work was funded by the Medical Research Council, Wellcome, Innovate UK, Guts UK, Swedish Research Council, European Research Council, European Union’s Horizon Europe and the Robert Bosch Foundation. Related links Read the full paper in Nature Genetics Research briefing in Nature Genetics Ramachandran research group StreatoSITE webpage Human Cell Atlas Tags CIR This article was published on Wednesday 14 October 2026
