Leaving home: Beta cells' way to maturity
Professor Henrik Semb and his group at the Danish Stem Cell Center have gained new insight into the molecular mechanism behind new born beta cells’ way to maturity. In depth knowledge about beta cell maturation is one of the fundamental ingredients in the development of future stem cell-based therapies in Diabetes as only correct and complete maturation will provide us with fully functional, glucose-responsive and insulin producing cells.
Beta cells are born in the developing pancreatic tubular epithelium, which gives rise to all endocrine and exocrine cells of the mature pancreas. Professor Semb and his team showed that the new born beta cells’ exiting and physical movement from their birth place within the epithelial tubes coincides with, but are independent of their maturation. “Our studies show that both the exiting and the maturation are regulated by the same signalling pathway called Cdc42/N-WASP, but very interestingly, we also found that the two important events occur independent of one another,” explains Henrik Semb.
The actual exiting comes about through a loosening of the adhesion between newly born beta cells and their neighbours. The cells are thereby released from the integrated epithelial layer, paving the way for their journey towards maturity. Concomitant with the exiting towards a life as part of the islets of Langerhans, Professor Semb and his team also show for the first time that mechanical forces within the cell - via the cytoskeleton – directly regulates maturation via specific gene expression changes.
“This new insight into the beta cell maturation process provides an important missing link in the efforts to generate fully functional, glucose-responsive and insulin producing cells from stem cells. Our long-term goal is to generate mature and fully functional beta cells which can be used in future stem cell-based therapies in Diabetes,” says Henrik Semb.
The result is published online on January 21, 2014 in the scientific journal Development in the article: Cdc42/N-WASP signaling links actin dynamics to pancreatic beta cell delamination and differentiation
Contact: Professor Henrik Semb, firstname.lastname@example.org or Research Coordinator Johanne Keiding, email@example.com, +45 20 56 00 63
Cdc42/N-WASP signaling links actin dynamics to pancreatic beta cell delamination and differentiation
Published on January 21, 2014 in Development, 141, 685-696, doi: 10.1242/dev.100297
Time lapse imaging: beta cell delamination, migration and clustering:
The movie show Time lapse imaging of Ins+ cells in Wt; MIP-GFP shows beta cell delamination, migration and clustering. The Ins+ cell (indicated with arrow) delaminates and migrates towards an extra-epithelial Ins+ cell cluster. The day of the harvest (E11.5) was marked day 0. Starting from day 5, the explants were imaged for about 17 hours.
Beta cells and Diabetes
Beta cells are the key player in diabetes: the cells are found in the pancreas, and are responsible for producing insulin, the hormone that controls energy transport in the form of glucose from the bloodstream to the muscles. In Type-1 diabetes, the immune system kills the beta cells, while in Type-2 diabetes, insulin sensitivity decreases making the body require more and more insulin, which the beta cells are unable to provide, eventually leading to beta cell failure.
Diabetes currently affects 366 million people worldwide. In Europe alone, the number of people with diabetes is estimated to be 52.8 million.