The technology used by the team produces a combination of different types of data for each individual cell. The kit that enables this has only been commercially available for two years, and the team is one of the first to publish research using it.
The first type of data they can produce is from the transcriptome – that is the RNA in the cell – which shows which genes are switched on and off. The second dataset uses an assay called ATAC-seq which tells researchers which parts of the genome are ‘open’. While the majority of our DNA is tightly wound up in our cells, some regions are open. These might be regions where regulatory elements, such as transcription factors, bind to switch on multiple genes.
In combination these give detailed information on not only on which genes are active (or ‘expressed’), but also how that is regulated.
James explains the importance of this knowledge. “This is a very fundamental thing, because if you want to make cells in a dish resemble human cells, changing expression of single genes is not enough, you need to drive change in a whole raft of genes. For that, understanding the regulation of expression is vital.”
The other technical innovation is in the spatial data. “We use the cell profiles that we’ve generated using these single-cell sequencing techniques. Then, we map those profiles to their spatial coordinates,” says James. This mapping technique has been developed over the last few years by Vitalii Kleshchevnikov and colleagues working in Omer Bayraktar’s group at the Sanger Institute. They created a computational tool, called cell2location, which combines single-cell sequencing data with spatial information, to visualise the relationships between cells and better understand tissue biology.
Speaking in 2022, Omer said, “I’m very excited about the potential for cell2location to change the way we observe life at a molecular level. Now we have a tool that’s better than a microscope and can provide us with more detail than we could have ever imagined.”