Studying the pancreas, cell by cell

Scientists from the Berlin Institute of Health (BIH) and Charité – Universitätsmedizin Berlin are coordinating an international project on the single-cell analysis of the human pancreas. The project is part of a global undertaking – known as the Human Cell Atlas – to molecularly describe and map the human body one cell at a time. The aim is to understand what constitutes a healthy body, to discover previously unknown details about healthy and diseased tissue, and thus to help develop new and more precise diagnostic and therapeutic approaches. The European Union is supporting the Horizon 2020 project ESPACE to the tune of €5 million, with €1 million going to Berlin. The project kicks off on January 1, 2020.

The pancreas performs important functions in the human body. It controls blood sugar levels through the production of hormones such as insulin and glucagon in its islet cells. It also aids digestion by producing enzymes in its gland cells and secreting these into the small intestine. The enzymes break down proteins, carbohydrates and fats into their basic components, making them ready for use by the body. So it is no surprise that pancreatic disturbances have severe and immediate consequences: If insulin production stops working, then diabetes develops. If gland cells become overactive, the result is an inflammation of the pancreas, known as pancreatitis, or, in the worst case, pancreatic cancer.

“For this reason, we have long been interested in studying in detail this important human organ,” explains Professor Roland Eils, chair and founding director of the Digital Health Center at the BIH and Charité. Eils coordinates the pancreas subproject within the Human Cell Atlas Initiative. “It is, however, tricky to isolate the molecular components of the gland, because the digestive enzymes work very fast and quickly break down, for example, ribonucleic acid, or RNA.” In an international pilot project of the Human Cell Atlas, which was funded by the Chan Zuckerberg Initiative, Eils and his colleagues have therefore figured out how to carefully handle and process the individual pancreatic cells. “This preliminary work has made it possible for the pancreas sub-project to be incorporated into the global Human Cell Atlas initiative,” reports Eils.

In the current project, the scientists plan to closely examine the around 20 different known cell types in the pancreas – and possibly discover unknown cell types. A total of ten project groups from Germany, the Netherlands, Spain, Sweden, Israel and Italy will also study gene activity by analyzing the messenger RNA from the cell nucleus and the proteome, the set of all proteins in the individual cells. The material will come from organs removed from patients, brain-dead donors and deceased fetuses, thus enabling the scientists to compare diseased and healthy tissue and to track the development of the pancreas. Some 100,000 cell nuclei from different regions will be individually analyzed per organ – a total of three million cells overall.

“Such a mammoth project can only succeed if there is a joint effort by numerous partners with different areas of expertise,” says Eils. “Here experts from medicine, biology, mathematics, computer science, chemistry and physics will work together.” The actual analysis of the RNA from the cell nuclei and the spatial mapping will take place in Berlin. With the help of special microscopes and molecular staining methods, the group led by Dr. Christian Conrad from the Digital Health Center can determine exactly where in the pancreas each cell type originates. Jürgen Eils, brother and colleague of Roland Eils, and his team at the Digital Health Center will bring together and evaluate the data from the international sub-projects.

The pancreas project is a sub-project of the global Human Cell Atlas initiative, in which researchers around the world have joined forces to profile every single cell in the human body. The aim is to understand the processes in a healthy body in order to be able to better diagnose, treat and prevent diseases. “The Human Cell Atlas project is certainly one of the most promising projects in the life sciences field,” says Eils. “It is comparable to the Human Genome Project, which saw scientists around the world work together for 30 years to sequence the complete human genome. Similar to when the Genome Project got underway, the Human Cell Atlas poses a herculean task that can’t be accomplished with today’s methods. But our vision here is to make a significant contribution to understanding how human life functions.”

The pancreas project is the only one of the six European Human Cell Atlas initiatives that is being coordinated in Germany.