Single-cell RNA sequencing pinpoints cell that helps liver healing process

A type of cell responsible for repairing damaged liver tissue has been uncovered for the first time by a team of scientists.

The study, published in Nature, showed how these new-found cells migrate to the site of damage, providing new insights into the way the liver heals itself. The authors say the findings could spur the development of new therapies that harness the liver’s unique capacity to regenerate.

During acute liver failure, the organ’s ability to repair and regenerate is often overwhelmed, with patients requiring an emergency liver transplant to regain liver function.

Scientists from the University of Edinburgh studied human liver tissue from patients with acute liver failure for signs of cell proliferation and regeneration following the rapid loss of liver function.

They found that a significant proportion of cells retained the ability to multiply. There were, however, still substantial areas of damage in the patients’ livers, suggesting that processes other than cell proliferation are critical during regeneration.

The research team profiled the genes within every liver cell in both healthy and regenerating human liver tissue to better understand the regeneration process, using a technique called single-cell RNA sequencing.

The findings uncovered a previously undetected population of wound-healing liver cells that emerge during human liver regeneration to aid recovery.

Working with University of Glasgow scientists at the Cancer Research UK Scotland Institute, the team used special imaging techniques in mice to view the wound-healing cells in action.

Researchers from the UCL Institute for Liver & Digestive Health and the Royal Free Hospital then provided important clinical validation of the novel mechanism of liver repair in humans.

Professor Jalan said: “We investigated whether the ‘liver repair’ mechanisms that the team from Edinburgh and Glasgow discovered in animal models also occurred in humans, and found that the mechanisms were present in patients with severe acute indeterminate hepatitis. This provides evidence that the observations made in the study are likely to be clinically relevant for the treatment of liver diseases in humans.”

During liver regeneration, so-called leader cells appear at the edge of the healthy tissue, dragging the tissue together to close the wound – similarly to how skin heals after a cut.

Imaging also revealed that the population of healing liver cells appears before cell proliferation begins.

Widespread infection is a major concern following acute liver failure. Bacteria from the gut can escape into the liver when the liver is damaged. This can lead to sepsis if the liver is unable to clear the infection.

The liver may prioritise the healing of wounds before cell proliferation to restore the gut-liver barrier and prevent the spread of bacteria, experts say.

Professor Neil Henderson, principal investigator of the study from the University of Edinburgh’s Centre for Inflammation Research, said: “Cutting-edge technologies have allowed us to study human liver regeneration in high definition for the first time, facilitating the identification of a cell type that is critical for liver repair.

“We hope that our findings will accelerate the discovery of much-needed new treatments for patients with liver disease.”

SourceUniversity College London

Matchett KP, Wilson-Kanamori JR, Portman JR, Kapourani CA, Fercoq F, May S, Zajdel E, Beltran M, Sutherland EF, Mackey JBG, Brice M, Wilson GC, Wallace SJ, Kitto L, Younger NT, Dobie R, Mole DJ, Oniscu GC, Wigmore SJ, Ramachandran P, Vallejos CA, Carragher NO, Saeidinejad MM, Quaglia A, Jalan R, Simpson KJ, Kendall TJ, Rule JA, Lee WM, Hoare M, Weston CJ, Marioni JC, Teichmann SA, Bird TG, Carlin LM, Henderson NC. (2024) Multimodal decoding of human liver regeneration. Nature [Epub ahead of print]. [article]

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