21 May

Mapping cell-cell interactions with new methodology

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Researchers of the Hubrecht Institute (KNAW) have developed a new method to map the network of cellular interactions. With this method, new cell groups and interactions can be discovered in a variety of organs. A team of researchers of the Van Oudenaarden group write this in an article that is published today in Nature Methods.

Cells and their functions are influenced by their niche – the network of cells in the nearby environment. When studying niches in an organism, researchers have to make assumptions of the cells of interest, possibly impeding the potential discovery of new groups of cells. Scientists of the Hubrecht Institute, led by Alexander van Oudenaarden, have developed a method to discover new niches. This method is based on mapping physical cell-cell interactions using single-cell mRNA sequencing.

Individual cells
Single-cell mRNA sequencing is a technology that allows researchers to determine the gene expression profile of individual cells. First, a single cell is sorted, its mRNA is multiplied and the material receives a molecular barcode. Next, the mRNA of various cells can be combined and analyzed. The barcode allows researchers to trace back the data to the original cell. Therefore, these experiments give us information on the genes expressed by each researched individual cell.

Interactions
As a model for their research, first author Jean-Charles Boisset and his colleagues used the bone marrow of the mouse. The bone marrow is a niche for hematopoietic cells – the source of all blood cells. It is, however, unclear in what way these cells are distributed in the bone marrow. Using micro dissection and single-cell mRNA sequencing, the researchers discovered interactions between various cells: promyelocytes (precursors of granulocytes) and plasma cells. Megakaryocytes (precursors of platelets) and neutrophils interacted as well. Next, Boisset and his colleagues applied this method successfully to the intestinal crypt and discovered interactions between Lgr5 stem cells and hormone producing Tac enteroendocrine cells.

Mapping niches
According to Boisset and his colleagues, this research can be an expansion to all developments in the field of transcriptomics – the techniques used to study an organism’s transcriptome, the sum of all their RNA transcripts. After all, although it might be possible to recognize all cell types present in a niche, researchers will still not be able to map the interactions between them. With their method, they call ProximID, the researchers succeeded in predicting interactions in the bone marrow niche. They expect that ProximID will be of value in mapping other niches as well.

Mapping the physical network of cellular interactions
Jean-Charles Boisset, Judith Vivié, Dominic Grün, Mauro Muraro, Anna Lyubimova, Alexander van Oudenaarden
Nature Methods, DOI: 10.1038/s41592-018-0009-z

Alexander van Oudenaarden is director and group leader at the Hubrecht Institute, professor of Quantitative Biology of Gene Regulation at the UMC Utrecht and the Faculty of Science at Utrecht University, and Oncode Investigator. His group uses a combination of experimental, computational, and theoretical approaches to quantitatively understand decision‐making in single cells, with a focus on questions in developmental and stem cell biology.

About the Hubrecht Institute
The Hubrecht Institute is a research institute focused on developmental and stem cell biology. It encompasses 20 research groups that perform fundamental and multidisciplinary research, both in healthy systems and disease models. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), situated on the Utrecht Science Park ‘De Uithof’. Since 2008, the institute is affiliated with the University Medical Center Utrecht, advancing the translation of research to the clinic. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL). For more information, visit www.hubrecht.eu.

About the Royal Netherlands Academy of Arts and Sciences (KNAW)
The Royal Netherlands Academy of Arts and Sciences is the forum, conscience, and voice of the arts and sciences in the Netherlands. It promotes quality in science and scholarship and strives to ensure that Dutch scholars and scientists contribute to cultural, social and economic progress. As a research organisation, the Academy is responsible for a group of fifteen outstanding national research institutes. 

About Oncode Institute
Oncode Institute is an independent institute whose goal is to translate fundamental insights about cancer to improved and more affordable care for patients as efficiently as possible. A team of renowned cancer researchers working in The Netherlands has joined forces within a mission-driven institute focusing on three pillars: excellent research, intensive collaboration and powerful valorization. The Dutch Cancer Foundation invests, together with the Dutch ministry of Economic Affairs & Climate Policy, the ministry of Education Culture & Science, the ministry of Health, Welfare & Sport, Health~Holland, NWO and ZonMw, a total of €120 million in Oncode Institute until 2022.