Surprised organ researchers: some cells remain single – others create families

Breaking new ground 29. okt 2017 2 min Professor Anne Grapin-Botton Written by Morten Busch

In the future, artificial organs can be created to replace a damaged organ or to produce vital hormones in a laboratory. Researchers do not yet understand how organs develop from a few stem cells into complete organs of many types. New research published in Nature Communications shows surprisingly that some cells generate daughter cells while half remain single.

The dream of being able to replace damaged organs is getting ever closer. Researchers have learned to cultivate stem cells and get them to grow and differentiate. Using 3D printers, a technique has even been developed to print biological material using stem cells. Currently, however, more knowledge is required on how organs are created and develop to be able to copy the body’s manual. A research group has therefore attempted to examine how the human pancreas forms in the embryo stage.

“Organs develop by individual cells growing and dividing and thereby producing offspring. The surprising thing in our study was seeing how much more active some cells are than others. Some stem cells divide many times, whereas others remain single throughout the process,” explains Anne Grapin-Botton, Professor, Novo Nordisk Foundation Center for Stem Cell Biology.

Helps cells to grow and divide

The researchers had to go through a very time-consuming process to discover the mechanism by which the pancreas is created in a mouse embryo. Following the destiny of an individual cell actually required staining one and only one cell at a time with a fluorescent marker. This enabled the researchers to monitor the progress of each individual cell to determine whether it divided or not. The process had to be repeated more than 100 times to get an overview of the diversity of the cells’ destinies.

“We definitely had not counted on such great differences between the destinies of the individual cells. In the beginning, it was not obvious which cells would have large families and which would remain single. The ability of cells to be able to divide and develop is very important in succeeding in cultivating artificial organs, and we therefore hope to learn how to recognize these organ-creating cells.”

The cells that did not have daughter cells or only very few also seemed to have roles in creating the pancreas. At least this is what the researchers believe based on discovering that nearly half the cells produced virtually no daughter cells.

“These cells produced hormones. Since only about 1% of the cells in a fully developed pancreas produce hormones, we assume that these cells, and possibly the hormones they make, have a function in developing the organ, presumably by helping the surrounding cells to grow and divide.”

Towards curing diabetes

Even though cells had different fates, only a few could be predicted by observing their initial differences in gene expression. With help from physicists from the Niels Bohr Institute of the University of Copenhagen, who used computer models, the researchers showed that the observations can be explained by the cells making decisions later with certain probabilities.

“We think that the cells communicate and send signals to each other. Based on these, they “agree” on who does what. This communication is probably based on chemical signals that we definitely do not know yet. But succeeding in creating organs and specific cell types requires understanding their language.”

The researchers have previously created micro-organs – miniature versions of the real organs in laboratories that can imitate the role of real organs in the body, such as producing insulin in the pancreas. The new discovery provides researchers important knowledge in continuing their work towards the ultimate goal.

“In the long term, we hope to be able to develop complete, functioning organs that may be used to save people’s lives or test better drugs. Nevertheless, even with our current results we are beginning to understand several processes that can help us to control and create new beta cells for people with diabetes, with the hope of curing them instead of treating them for life.”

Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis” has been published in Nature Communications in collaboration between DanStem and the Niels Bohr Institute of the University of Copenhagen as one element in the Center for Stem Cell Decision Making (StemPhys) supported by the Danish National Research Foundation. Anne Grapin-Botton is a Professor affiliated with the Novo Nordisk Foundation Center for Stem Cell Biology of the University of Copenhagen. The Novo Nordisk Foundation has awarded research grants of almost DKK 700 million to the Center in 2010–2017.

Anne Grapin-Botton has a background in developmental biology and initially studied nervous system and endoderm development. Her laboratory is currentl...

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