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21.11.2024

Sugar coats set apart cells from different organs, new method reveals

Complex sugar molecules, the glycans, coat all cells and give them tissue-specific identities. Scientists from the group of Josef Penninger working at IMBA and the MedUni Wien, together with researchers at the University of Natural Resources and Life Sciences (BOKU), developed a new method to study the structure of glycans at an unprecedented scale. This discovery opens new perspectives for biomedicine and could deepen our understanding of glycans in healthy and diseased organs. Their findings were published on November 9th in Nature Communications.

Fluorescence microscopy image of a murine kidney. Two glycan structures (Antennary fucosylated glycans and sialylated glycans) are visualized in red and green, respectively. Nuclei are shown in blue. ©Stefan Mereiter/IMBA

Complex sugar structures, the glycans, decorate the surface of cells, enabling cells to interact with one another and their environment; immune cells, for example, rely on glycans to identify and travel to lymph nodes. 

Despite their critical role in cell function, little is known about the diversity of glycans and the range of glycans found in different organs. Much remains unknown as glycans are difficult to study experimentally and a complete characterization of glycans is usually impossible by a single method. Now, a team of scientists working at IMBA, the Medical University of Vienna (MedUni Wien), and at the University of Natural Resources and Life Sciences (BOKU) have developed an innovative, scalable approach to study structural differences in glycan chains. The scientists aimed to find out how large the differences between the glycan chains that shape the liver, for example, and those that shape the brain are. 

The newly developed method allows quick processing and interpretation of data from state-of-the-art glycan analysis of twenty different mouse tissues. Combining the data obtained with their knowledge of anatomy and physiology allowed the researchers to create the most detailed map of mammalian glycans to date.  

“We first had to develop a completely new way of evaluating data in order to be able to handle the analysis. In fact, we managed to carry out a process that could normally take many months in just a few weeks,” explains Stefan Mereiter, co-first author of the study and senior postdoctoral researcher in the lab of Josef Penninger. However, the most exciting thing about this new approach was that, unlike conventional manual analyses, the method was able to automatically recognize and characterize even unexpected glycan structures. 

Using the new method, the researchers uncovered that each tissue features a unique glycosylation pattern, which could help understand the unique identities of organs. Moreover, the researchers uncovered new, previously undetected glycan structures. “We were aware that glycans are complex biomolecules, but we were all surprised by how incredibly diverse glycans can be in a single organism,” says Johannes Helm from the Institute of Biochemistry at BOKU.  

The newly developed method revealed an unprecedented level of molecular diversity in glycan coatings across organs. “Our findings open up new possibilities to better understand the complex role of glycans in both healthy and diseased organs,” says Stefan Mereiter. “Decoding the full diversity and function of glycans in different cells and organs will be crucial to unraveling the true complexity of biological systems and could lead to major advances in biomedical research.”