Dr. Nikolay Ninov, group leader at the DFG research center for Regenerative Therapies Dresden (CRTD), Cluster of Excellence at the TU Dresden, and Paul Langerhans Institute Dresden (PLID), and his group developed a system called "Beta-bow", which allows the history of β-cells to be traced by genetic bar-coding and multicolor imaging.
Tracing the history of individual cells in the developing organism can reveal functional differences among seemingly uniform cells.
Tracing the history of individual cells in the developing organism can reveal functional differences among seemingly uniform cells. This knowledge is important for defining the characteristics of highly regenerative cells in order to target them for cellular therapies, as well as to prevent the formation of unfit cells, which compromise the overall health of the organism. The study introduced here presents a new method for tracing the history of β-cells, which perform the essential function of secreting insulin in response to glucose. The authors traced β-cells with regards to their proliferation, function and time of differentiation in the zebrafish. The study shows that β-cells with different developmental histories co-exist together, which leads to the formation of dynamic sub-populations that differ in their potential for undergoing proliferation and performing functional tasks. The study also reveals the onset of β-cell function in zebrafish, which opens new avenues to investigate how β-cells acquire a functional state using this powerful genetic model.
Recently, the heterogeneity among β-cells has become evident, and it is believed that this heterogeneity might play a role in the progression of diabetes. "For example, even 20 years after the onset of Type 1 diabetes, some β-cells can survive in the pancreas, perhaps because these cells are different from the rest, which allows them to hide from the immune system and to escape autoimmune destruction", Nikolay Ninov says. The ability to directly visualize the evolution of β-cell heterogeneity in zebrafish will help to understand the dynamic regulation of β-cell sub-populations at the molecular level. This knowledge is of crucial importance for the subsequent development of effective strategies for β-cell regeneration and protection in diabetes.
"As a next step, we will use our model and cell tracing methods to understand the signals that instruct β-cells to acquire a functional state. In particular, we found that in zebrafish this process takes only a few days after the birth of the cells, whereas it is difficult to achieve the formation of functional β-cells from human stem cells in vitro. Thus, our hypothesis is that the in vivo environment in the zebrafish pancreas provides powerful signals for rapid β-cell functional maturation. We will now identify these signals, as this knowledge can help to produce functional human β-cells in vitro for transplantation purposes", Nikolay Ninov explains.