Summary
- First-of-its-kind pediatric liver atlas is helping researchers uncover how liver disease develops in children, paving the way for better treatments and care
- Study found that comparing a child's liver to an adult's can miss key disease signals, indicating the need for pediatric liver data
Scientists studying liver disease have lacked a clear understanding of what a healthy pediatric liver looks like at the cellular level.
A study led by researchers at UHN is finally filling that knowledge gap, uncovering key differences between the liver of a child and an adult.
Developed with collaborators at the Hospital for Sick Children and the University of Toronto, the study led to the creation of the
first-of-its-kind single-cell atlas of human pediatric livers — a detailed “cell-by-cell map” that reveals how the liver works in children at a much deeper level than before.
By analyzing tens of thousands of individual liver cells, the team discovered that pediatric livers are not just smaller versions of adult livers. Instead, they function differently, particularly in relation to the immune system and how it responds to infection, injury and signals from the gut.
“When scientists compare a diseased pediatric liver to a healthy pediatric liver, they’re able to see specific signals that wouldn’t have come up if they had made the comparison with a healthy adult liver,” says Dr. Sonya MacParland, co-senior author of the study and research director at UHN's Ajmera Transplant Centre, and professor in the departments of immunology, laboratory medicine and pathobiology at the University of Toronto.
“Part of that is because there's so much inflammation in the adult liver.”
Having this data may help researchers understand how liver disease develops in children, leading to more accurate diagnosis and targeted treatments.
One of the study’s most important findings was that comparing livers in children to adults can miss critical disease signals, reinforcing the need for pediatric-specific data.
Creating the map for pediatric liver care
The liver plays a vital role in the body, helping to regulate metabolism, support immune function and process nutrients. When diseases damage the liver, it cannot perform these functions effectively, leading to serious health complications.
Although liver disease research has traditionally focused on adults, children experience many of these conditions differently.
To create the atlas, researchers brought together expertise in pediatric hepatology, transplantation, pathology, immunology, surgery and research.
“Having a multidisciplinary, collaborative approach was essential to know what the data showed and what it meant in the context of a real liver,” says Dr. MacParland.
Instead of looking at liver tissue as one large organ, researchers examined individual cells, allowing them to identify which cell types are present and how each type performs.
“Basically, we work on the liver and dissociate it, meaning we break it down to look at individual cells that were all attached to each other,” explains Dr. Rachel Edgar, co-lead author of the study and a Canadian Institutes of Health Research-funded postdoctoral researcher at UHN.
Researchers then analyzed the gene activity in each cell to create the atlas, a detailed map that illustrates what cells make up the pediatric liver and how each cell functions.
The study found that pediatric liver immune cells are naturally more active than those in adult livers. This may allow children’s livers to react faster and more strongly to what’s happening in the body, such as infections, gut signals and growth changes.
The team also compared healthy pediatric livers to livers with a serious condition called intestinal failure–associated liver disease (IFALD). The comparison revealed early signs of scarring (fibrosis) and specific immune changes linked to IFALD at a precise, cellular level.
Impacting the future of research and treatment
The pediatric liver atlas is enabling new studies and discoveries focused on liver diseases affecting children.
Mary Vyas, a patient partner and research associate at UHN, has already seen this impact firsthand.
She is involved with a research project focused on primary sclerosing cholangitis (PSC), a rare, chronic liver disease her child was diagnosed with as a teenager. Currently, the only proven treatment option for the disease is a liver transplant.
“PSC is a devastating diagnosis because you can’t always be sure you’ll have access to a liver transplant. Every year, people die from not being able to get a transplant or being too sick to survive a transplant,” says Vyas.
By providing a detailed picture of what a healthy pediatric liver looks like, the atlas is helping advance research into diagnosing and treating PSC in children, bringing new hope to patients and families facing the disease.
“We're discovering how PSC presents differently in the pediatric liver versus the adult liver, and how can we possibly treat children with this disease in the most effective way,” says Vyas.
“This study is super exciting for patients with PSC, but also for any pediatric liver disease that has unanswered questions or unmet needs.”
Accessible resource for open science
The pediatric liver atlas also serves as a foundation that other researchers can build on.
Data from the study was made publicly available prior to publication with the aim to accelerate discovery and research worldwide.
“We really believe in this open science approach because the data is not owned by any particular researcher. It's owned by everyone,” says Dr. MacParland.
“This is the first time that we've openly shared the data before it's ever published, so that means anyone could access it whether they were a study collaborator or not.”
Researchers hope that by sharing the data, further studies will help improve health outcomes for pediatric patients facing liver diseases.
