How does the developing pancreas in an embryo 'know' which cells are to produce insulin and which cells are to have other assignments? Researchers need to understand this if they want to be able to treat type-1 diabetes with stem cells developed into insulin-producing beta cells. At Lund University scientists have uncovered pioneering new knowledge, and are publishing it in the journal Cell.

Cell is one of the most highly esteemed journals in the field of biomedicine, and the competition to get published there is brutal.

"It's extremely uncommon for a research team from Lund to have an article published in Cell. We have also been asked to make the video that is uploaded to YouTube in connection with each new issue of Cell. This is obviously a great achievement," says stem cell and diabetes researcher Henrik Semb.

His research team has studied two fundamental scientific questions: One is how tubes are formed in organs where they fulfill vital functions (some examples are the fact that the kidneys filter urine in tubes, blood vessels transport blood in tubes, and the lungs transport air in tubes). The other is the question of how the differentiation of cells the development of immature cells into various mature cells - is related to tube formation.

"Scientists have long known that both processes take place at the same time in an embryo, but we didn't know whether they are connected," says Henrik Semb.

According to the Lund researchers, they are. They can explain step by step how some cells in the developing pancreas form tiny cavities, and how these cavities join together and eventually create a system of tubes. They also explain how cells that end up in different parts of this tube system become exposed to different environments, making them develop in separate ways. Some end up producing insulin, while others produce enzymes that digest food in the intestines, and still others participate in the tube construction itself.

The Lund team has also found that a gene called Cdc42 is fundamental for these processes. This was demonstrated in so-called knock-out mice where this gene had been removed. Without Cdc42 no tubes are formed in the pancreas, and with no tubes the environment that dominates is the kind that is normally found around cells that produce enzymes. The Lund scientists show in their 11-page article how this leads to a pancreas that only generates enzyme-producing cells, at the expense of the important insulin-producing beta cells.

These findings provide fundamentally important new knowledge in basic science that may be applied in future medical treatments. Research on stem cell treatment of type-1 diabetes can now take several steps forward, with the new understanding of how immature cells develop into beta cells. The results will also help the insight into diseases where organ failure is due to cyst formation in tubes, such as in the kidneys and the liver.

Henrik Semb's research team has studied tube formation, cell differentiation and the role of Cdc42 in these processes for many years. This is the type of dedicated work required to be published in a major Cell article.

"It has often been tempting to pause and publish the various partial findings in other journals. But we have had a superb team that has managed to sustain its enthusiasm and energy," he says.

Source: Lund University

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