25 May 2021

New miniature organ to understand human pancreas development

discovery

The Grapin-Botton group, UCPH DanStem/ MPI-CBG, Dresden establish human pancreas culture system.  Nature Communications. doi: 10.1038/s41467-021-23295-6.

The pancreas is a little organ behind the stomach and has two main functions – digestion and blood sugar regulation. How the human pancreas develops has been relatively unexplored for ethical and practical reasons. Researchers from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, the Novo Nordisk Foundation Center for Stem Cell Biology (DanStem) in Copenhagen, Denmark, and several other International collaborators, including the LCSB – Luxembourg Centre for Systems Biomedicine in Luxembourg were now able to establish a human pancreas miniature organ in cell culture. Another result of the study is also an atlas of single cells in the human fetal pancreas, which allows researchers to see which genes are expressed in the different cell types during development. This miniature organ and the atlas could offer insights into human syndromes impairing pancreas development and can help in generating replacement beta cells for diabetes therapy.

Even though the pancreas is a little organ, sitting behind the stomach, it is an essential organ producing digestive enzymes and hormones, notably insulin and glucagon. To study the development of this vital organ, Anne Grapin-Botton, a director of the MPI-CBG and former professor at the DanStem, developed in past studies culture methods that allow mouse pancreas cells to grow in three-dimensional conditions, forming tree-like structures that resemble a miniature mouse pancreas. Those miniature organs are also referred to as organoids. The development of the human pancreas in embryos has been challenging to research and there was little information available on how its cells develop in 3D.

Our cell culture system enables us to study human pancreas development in three-dimensions. Diseases like diabetes can have their origin already during the development of a fetus. With this new three-dimensional miniature organ, we can get more insight into the human pancreas development.

Anne Grapin-Botton.  

Carla Gonçalves, a doctoral student in the research lab of Anne Grapin-Botton at Danstem, worked together with colleagues in both DanStem and MPI-CBG to develop a similar culture system for human pancreas cells in order to study the developing human pancreas. The researchers then compared these newly generated human pancreas organoids and human pancreas cells in traditional flat cell culture to a reference single cell transcriptome of the human fetal pancreas. This single cell transcriptome atlas shows all the genes expressed in each cell during development, as only a subset of the genetic code is converted into RNA molecules and then proteins.

When comparing the two cell culture systems, we found that the pancreatic progenitor cells in the three-dimensional cell culture system  are more similar to the cells in the human fetal pancreas. The method to generate the miniature human pancreas is very robust, so it will allow us to explore many questions related to human pancreas biology in the future.

Doctor Carla Gonçalves

“Indeed, organoids can be observed with microscopes as they develop and easily subjected to experiments, which we are doing at the MPI-CBG,” adds Anne Grapin-Botton. Colleagues from the LCSB – Luxembourg Centre for Systems Biomedicine used the data generated from the human fetal pancreas to study how cells communicate, using a new computational model enabling to trace which cells produce which signal and which ones receive it.

We now have a benchmark how a normal human pancreas should develop and study how diabetes may occur when development goes wrong. We can also study how the beta cells that make insulin are formed to produce them more efficiently for future cell therapies of diabetes.

Anne Grapin-Botton.  

Gonçalves, C. A, Larsen, M., Jung, S., Stratmann, J., Nakamura, A., Leuschner, M., Hersemann, L., Keshara, R., Perlman, S., Lundvall, L., Langhoff Thuesen, L., Hare, K. J., Amit, I., Jørgensen, A., Kim, Y. H., del Sol A. and Grapin-Botton, A. (2021) A 3D system to model human pancreas development and its reference single cell transcriptome atlas identify signaling pathways required for progenitor expansion. Nature Communications. doi: 10.1038/s41467-021-23295-6

Credits @ Rashmiparvathi Keshara

About the Novo Nordisk Foundation Center for Stem Cell Biology (DanStem)

The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem) was instituted in 2011 as an international research center for basic stem cell and developmental biology with a grant from the Novo Nordisk Foundation. DanStem is solving complex problems in stem cell and developmental biology, spanning early embryonic development and organogenesis through advanced disease development and cell or drug-based therapies. The center is part the Faculty of Health and Medical Sciences of the University of Copenhagen.

www.danstem.ku.dk

About the MPI-CBG

The Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), located in Dresden, is one of more than 80 institutes of the Max Planck Society, an independent, non-profit organization in Germany. 550 curiosity-driven scientists from over 50 countries ask: How do cells form tissues? The basic research programs of the MPI-CBG span multiple scales of magnitude, from molecular assemblies to organelles, cells, tissues, organs, and organisms. The MPI-CBG invests extensively in Services and Facilities to allow research scientists shared access to sophisticated and expensive technologies.

www.mpi-cbg.de

About the LCSB – Luxembourg Centre for Systems Biomedicine

The LCSB is part of the University of Luxembourg and accelerating biomedical research by closing the link between systems biology and medical research. Collaboration between biologists, medical doctors, computer scientists, physicists, engineers and mathematicians is offering new insights in complex systems like cells, organs, and organisms. These insights are essential for understanding principal mechanisms of disease pathogenesis and for developing new tools in diagnostics and therapy.

wwwde.uni.lu/lcsb