New miniature organ to understand human pancreas development

Understanding human pancreas during development

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. Now, a collaborative effort between Antonio del Sol, who leads the Computational Biology groups at CIC bioGUNE and the Luxembourg Centre for Systems Biomedicine (LCSB), and 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, as well as several other International research groups, led to the establishment of a human pancreas miniature organ in cell culture. In addition, the authors generated 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. Moreover, by leveraging a computational model of cell-cell communication, developed in Computational Biology groups at CIC bioGUNE, and the single cell expression atlas, important differences in the signals regulating human and mouse fetal pancreas development have been revealed. 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. 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. Culture methods that allow mouse pancreas cells to grow in three-dimensional conditions, forming tree-like structures that resemble a miniature mouse pancreas, also referred to as organoids, has been fundamental to start studying those phenomena. In this context, the cell-cell interactions that have been identified in the fetal pancreas can be instructive for devising new protocols to stabilize the state of the human organoids, thereby providing a source for the generation of insulin producing cells that could be used in cell replacement therapies.

Picture Caption:
A computational model unravels cell-cell interactions in human fetal pancreas development. Copyright: Sascha Jung.

Original Publication:
Carla A. Gonçalves, Michael Larsen, Sascha Jung, Johannes Stratmann, Akiko Nakamura, Marit Leuschner, Lena Hersemann, Rashmiparvathi Keshara, Signe Perlman, Lene Lundvall, Lea Langhoff Thuesen, Kristine Juul Hare, Ido Amit, Anne Jørgensen, Yung Hae Kim, Antonio del Sol, Anne Grapin-Botton: A 3D system to model human pancreas development and its reference single cell transcriptome atlas identify signaling pathways required for progenitor expansion. Nature Communications, 25 May 2021,  Doi: 10.1038/s41467-021-23295-6

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.

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.

About CIC bioGUNE
The Centre for Cooperative Research in Biosciences (CIC bioGUNE), located in the Bizkaia Technology Park, is a biomedical research organization conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies. CIC bioGUNE has been accredited as a “Severo Ochoa Centre of Excellence”, the highest level of recognition for centers of excellence in Spain.

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