Map for research into young pancreatic cells
Our pancreas consists of various cells that are very important in controlling our blood sugar. One of these genes in the pancreatic cells is neurogenin 3 (NEUROG3), a mutation of which can lead to diabetes. This gene is only active for a short time during the development of the pancreas, which is why its behaviour and dynamics, particularly in the context of human development, were previously unknown. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden and the Novo Nordisk Foundation at the University of Copenhagen have now used a special method to observe both the activity of the gene and the protein it forms in human pancreatic cells, thereby gaining a better understanding of the gene. This method makes it possible to link the dynamic behaviour of pancreatic cells, which could be observed in live recordings, with all the genes they produce. This makes it possible to better understand how the hormone-producing cells of the pancreas develop. This could pave the way for obtaining more of these cells for therapeutic purposes, for example for the production and transplantation of these cells in patients suffering from diabetes.
The different cells in the pancreas control our blood sugar, such as the beta cells that produce insulin. Insulin helps to lower our blood sugar. If these cells stop working or die, we can develop diabetes. During our body's growth, all these special cells are derived from a single cell type in the pancreas, the endocrine precursor of the pancreas. This cell type only uses a gene called NEUROG3 for a short time to fulfil its task.
The research group of Anne Grapin-Botton, Executive Director at the Max Planck Institute of Molecular Cell Biology and Genetics, together with colleagues from the Novo Nordisk Foundation at the University of Copenhagen, has set itself the goal of investigating these special cells in the pancreas that utilise the NEUROG3 gene in more detail and understanding how this gene behaves in individual cells.
Different gene activity
“We used special markers to see NEUROG3 in these cells. This allowed us to observe in live images how the cells move over a longer period of time," explains Belin Selcen Beydag-Tasöz, the first author of the study, and continues: "By looking at 2-D and 3-D models of the human pancreas, we found that the concentration of the NEUROG3 gene was different in the different cells. Some cells had a lot of this gene, others only a little. Surprisingly, despite these differences, all cells in which NEUROG3 was detectable formed cells that produced hormones. Another surprising result was that NEUROG3 works about twice as slowly in humans than in mice. This means that this gene needs more time to fulfil its task in humans than in mice.
The researchers used the method of long-term live imaging to observe a process that normally remains hidden in the womb. The brightness of the cells helped them to combine the activity of the genes with the behaviour of the cells. In this way, the research team found that another gene called KLK12 ensures that the cells move to form islets of Langerhans as soon as the NEUROG3 gene starts to work.
Anne Grapin-Botton, who led the study, summarises: „The cell culture systems we have developed to understand how cells form organs in human embryos are bearing their first fruits. In our study, we have learnt much more about how the activity of certain genes during embryonic development can lead to diabetes in later life. The results show that there is some flexibility in the control of NEUROG3 in the production of endocrine cells for future therapeutic applications in which these cells are transplanted into diabetic patients.
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