Pancreas cells retain traces of their fetal past

The pancreas performs two vital jobs at once. Firstly, it produces the enzymes needed to digest food, and secondly, the hormones that keep blood sugar in range, including insulin. When the second job fails, the result is diabetes, a disease affecting millions of people worldwide. Yet despite the pancreas’ central role in human health, scientists lack a complete picture of the cell types that make up the organ, how they form, or what happens to them under strain. 

Now, an international team of researchers has built one of the most comprehensive maps of the human pancreas cells to date. By analyzing more than four million cells and cell nuclei from pancreatic tissue donated by 57 individuals, the team investigated fetal development, healthy adult tissue, and tissue from people with type 2 diabetes. 

Cells that behave like fetal cells

The most surprising finding sits at a junction. Centroacinar cells lie where the enzyme-producing parts of the pancreas meet the ducts that carry those enzymes away. They are rare, and until now no one had described them as a population of their own. They also carry molecular features that normally vanish once an organ has finished forming.

That flexibility, which researchers call plasticity, may allow the cells to switch roles. The team suspects they help the pancreas cope with stress and possibly repair damaged tissue.

“The fetal data allowed us to identify the early cells that give rise to every other cell type in the pancreas,” says Dr. Valerie Vandenbempt, postdoctoral researcher at the University of Helsinki and one of the authors of the study. “That makes the atlas a useful starting point for anyone trying to replace or repair pancreatic tissue.”

Beta cells differ more than expected

Insulin-producing beta cells are essential for controlling blood sugar levels, but this study reveals that they are far from identical. The researchers identified several distinct beta-cell states, each characterized by their own patterns of gene regulation. In individuals with type 2 diabetes, these regulatory programs were altered, suggesting that the disease reshapes how beta cells function.

To understand how these beta cells respond to diabetes-related stress, the team also exposed healthy cells to high glucose levels. Different cell types responded in different ways, highlighting the complexity of the organ’s response to challenging conditions.

“ captures not only which genes are active in each pancreatic cell type, but also the mechanisms that switch them on and off,” says the research group leader Dr. Balboa. “Those differences may help explain why disease risk, progression and response to treatment vary from one person to the next.”

What the atlas cannot yet tell

The researchers are careful about what this implies. According to Dr. Balboa, the atlas is a reference, not a treatment. Two questions stand out: Tissue from 57 donors cannot represent the full range of human biology, so larger and more varied groups will be needed to see how age, sex, ancestry and lifestyle shape the pancreas. It is also unknown whether the beta cell changes seen in type 2 diabetes cause the disease, result from it, or reflect the body responding to metabolic strain.

The dataset is openly available , which is much of the point. Research groups anywhere can now compare healthy and diseased pancreatic tissue against a shared reference.

The work was done by the ESPACE consortium, part of the EU-funded Human Cell Atlas project, and coordinated by the Berlin Institute of Health at Charité (BIH). The Pancreas Development and Disease laboratory at the University of Helsinki made an instrumental contribution, and the research group leader Dr. Balboa is a shared first author of the paper.