As part of an international project, scientists from the Berlin Institute of Health (BIH) and Charité – Universitätsmedizin Berlin have genetically examined all cells of the human pancreas to determine their exact location within the organ and shed light on the relationships between individual cells. In doing so, they discovered previously unknown cell types that help to explain how this important organ functions and how pancreatic diseases develop. The project is part of the global Human Cell Atlas initiative, which aims to analyze all cells of the human body. The researchers have now published their results in the journal Gastroenterology.
“We wanted to create a resource for all researchers with an interest in the pancreas,” explains Professor Roland Eils, head of the international pancreas project and, as BIH Chair, founding director of the BIH and Charité Digital Health Center. “Our results will help those who study the endocrine component of the pancreas, which produces insulin and is responsible for the development of diabetes. But our findings are also relevant for scientists studying the gland’s exocrine component, which produces and releases digestive enzymes into the small intestine and is affected by pancreatitis or pancreatic cancer.”
Obtaining and examining pancreatic tissue is extremely difficult, as the digestive enzymes are very active and the organ runs the risk of digesting itself. It was therefore important for the scientists to prepare the tissue as gently and quickly as possible. Here, Eils and his team relied on international cooperation. “We received high-quality samples from colleagues in Stanford and Munich,” explains Christian Conrad, whose lab hosted the experiments and who is joint last author of the study together with Eils. “We then developed new protocols specifically for pancreatic tissue in our laboratory, which enabled us to obtain this type of data for the first time.”
Luca Tosti, a postdoc in Conrad’s lab and lead author of the study, applied various single-cell technologies in this mammoth project. “One technique involved isolating cell nuclei from frozen biopsies and measuring gene activity in each nucleus individually,” explains Tosti. “In total, we analyzed more than 120,000 cell nuclei. In addition, we performed so-called in-situ sequencing on the frozen tissue. This method tells us not only which genes are active in the various cells, but also how the cells are organized spatially and what relationships exist between the different cells.”
During their investigations, the team was able to divide exocrine pancreatic cells into three subtypes. A comparison of adult tissue with that of newborns showed an astonishing change in cell composition during development. “We were surprised to find that an organ previously regarded as relatively homogeneous has such a complex structure,” reports Eils. “By combining various biological and computational techniques, we have gained insight into intercellular communication in the human pancreas to an extent that has not previously been possible.”
Next, the researchers want to analyze samples from patients with diabetes or pancreatic tumors in order to better understand the causes of pancreatic diseases and to develop new 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 the BIH Digital Health Center in Berlin. The project kicked off on January 1, 2020.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. “Our vision 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.
More information about ESPACE can be found at: