New Single-Cell Atlas Reveals the Plasticity of the Human Pancreas
An international research team coordinated by the Berlin Institute of Health at Charité (BIH) has created the most comprehensive single-cell atlas of the human pancreas to date. As part of an EU-funded Human Cell Atlas project led by Professor Roland Eils, the team analyzed more than four million cells and cell nuclei from pancreatic tissue samples donated by 57 individuals.
The atlas spans key stages of pancreatic development and disease—from fetal development and healthy adult tissue to samples from people with type 2 diabetes. Using state-of-the-art single-cell and multiomics technologies, the researchers mapped gene expression, epigenetic regulation, and the spatial organization of pancreatic cells with unprecedented resolution.
Previously Unknown Cell Population Identified
The pancreas plays essential roles in metabolism and digestion and is also central to common diseases such as type 2 diabetes. However, many questions have remained about the diversity of human pancreatic cell types, how they change during development, and how they respond to disease-related stress.
One of the study's most significant findings is the discovery of a previously unknown population of highly plastic centroacinar cells, which form the interface between the acinar cells and the pancreatic ducts. Their "plasticity" is reflected in molecular characteristics reminiscent of early developmental stages, suggesting that these cells may be able to flexibly adapt their identity. This capability could play an important role in the pancreas' response to stress as well as in tissue regeneration.
The atlas also provides a detailed view of how endocrine cell lineages (which produce hormones that regulate blood glucose levels) and exocrine cell lineages (which produce digestive enzymes) develop. In addition, the team identified distinct epigenetic states among insulin-producing beta cells and uncovered characteristic changes in their regulatory programs associated with type 2 diabetes.
Distinct Responses to Metabolic Stress
Experiments exposing healthy pancreatic islets (the clusters of endocrine cells within the pancreas known as the islets of Langerhans) to elevated glucose concentrations revealed that different pancreatic cell types respond differently to metabolic stress. These findings provide new insights into how the cellular composition and function of the pancreas change under the conditions of metabolic disease.
"With this atlas, we can now follow the development of human pancreatic cells across the lifespan and observe how their identity changes in disease for the first time," says Professor Christian Conrad, MD, senior author of the study and head of the Intelligent Imaging research group at the Center of Digital Health at the Berlin Institute of Health at Charité (BIH). "These insights provide an important foundation for understanding the mechanisms underlying diabetes and, ultimately, for developing new regenerative therapeutic strategies."
A Resource for the International Research Community
The dataset generated through this project represents an important resource for the international research community. It will enable scientists worldwide to further investigate the cellular mechanisms underlying metabolic diseases, regeneration, and tissue plasticity.
In the long term, these findings could contribute to improved diagnostic approaches and support the development of innovative therapeutic strategies for type 2 diabetes as well as regenerative medicine.
