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Unprecedented 3D cellular maps enabled by cell2location tool developed by Wellcome Sanger Institute and collaborators

An astonishing new tool that will enable researchers to visualise and understand the relationships between individual cells in the human body has been created.

Called cell2location, it represents a major boost for the study of the human body at a single cell level and was developed by the Wellcome Sanger Institute, the German Cancer Research Centre and their collaborators.

The cell2location tool is able to create extraordinary cellular insights. Image: Omer Bayraktar (54405377)
The cell2location tool is able to create extraordinary cellular insights. Image: Omer Bayraktar (54405377)

Researchers have shown how it can be used to pinpoint the three-dimensional location of detailed immune cell types in the human gut and lymph node, and map the fine-grained structure of the mouse brain.

It is already in use in the Human Cell Atlas initiative led by the Sanger Institute to map every cell type in the human body and could one day replace microscope analysis as a means for pathologists to understand biopsies better.

The Human Cell Atlas and other projects are regularly finding previously undiscovered cell types using single cell sequencing to analyse individual cells, so that the genes they are expressing can be observed. This helps reveal subtle differences in cell function that define them.

But cells also communicate with each other and their relative positions are important in understanding how tissue functions at a molecular level.

Until now, single cell sequencing data could not be combined with spatial information at the scale required, but cell2location solves this.

It combines single-cell sequencing data and spatial transcriptomic data to visualise the relationships between cells and aid our understanding of tissue biology.

In analysis of the mouse brain, cell2location was able to detect subtle differences in neural cells called astrocytes down to as few as 10 different genes, identifying rare astrocyte subtypes never previously described.

It also mapped these, including one rare subtype that accounted for just 41 cells out of 40,000, to a specific location within the tissue.

Dr Oliver Stegle, a senior author of the paper published in Nature Biotechnology, from the Wellcome Sanger Institute, the German Cancer Research Center and the European Molecular Biology Lab, said: “The fact that cell2location was able to identify and spatially map previously undescribed astrocyte subtypes in the mouse brain demonstrates the remarkable sensitivity of our approach. Combined with a precise location for these rare subtypes, researchers now have access to a wealth of information with which to begin unravelling the role these cells play in the overall functioning of the brain.”

In future, using a single cell approach in pathology could also provide much more detailed information about what has gone wrong at a molecular level in diseases like cancer, which will aid in-depth studies such as clinical trials.

Dr Omer Bayraktar, a senior author of the paper from the Wellcome Sanger Institute, said: “I’m very excited about the potential for cell2location to change the way we observe life at a molecular level. I always thought that mapping tissues would remain in the realm of histology, which is limited in what it can reveal. Now we have a tool that’s better than a microscope and can provide us with more detail than we could have ever imagined.”

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