Rainbow colors reveal cell history: Uncovering β-cell heterogeneity by tracing developmental origins
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. The results of this study are now published in the scientific journal Nature Communications.
Zebrafish β-cells labeled using the Beta-bow system through the combinatorial expression of fluorescent proteins, allowing the developmental history of β-cells to be traced during islet growth.
© Ninov lab
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.
The project, which was envisioned about 3.5 years ago, was led by CRTD Postdoc Sumeet Pal Singh. In addition, Sharan Janjuha (PhD-student, DIGS-BB) established the assay for calcium imaging. Additional researchers include collaborators from Japan (Daiichi Sankyo Co.,Ltd), the UK (Oxford University) and Germany (CRTD).
“Curiosity, and the drive to make an original contribution towards a cure for diabetes by learning more about the basic biology of β-cells” motivates Nikolay Ninov in his daily work. Since 2013 Nikolay Ninov has been a Group Leader for “β-cell biology and regeneration” at the CRTD and the Paul Langerhans Institut Dresden (PLID) of Helmholtz Zentrum München at University Hospital Dresden and Medical Faculty Carl Gustav Carus of TU Dresden - a partner of the German Center for Diabetes Research (DZD). In 2008, Nikolay Ninov completed his PhD at the University of Barcelona (Spain, Parc Cientific de Barcelona). After that he worked as a Postdoc at the University of Toronto (Canada, Department of Cell and Systems Biology, 2008-2009), the University of California at San Francisco (USA) and the Max Planck Institute for Heart and Lung Research in Bad Nauheim (Germany) (2009-2013).
Title: Different developmental histories of beta-cells generate functional and proliferative heterogeneity during islet growth
Franziska Clauß, M.A.
Phone: +49 351 458 82065
Franziska Clauß | idw - Informationsdienst Wissenschaft
New RNA sequencing strategy provides insight into microbiomes
17.12.2018 | University of Chicago Medical Center
Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland
Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.
Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
17.12.2018 | Physics and Astronomy
17.12.2018 | Architecture and Construction
17.12.2018 | Life Sciences