Health Science Reviews

by Michael Goldschagg

Most of us are aware that each cell in every living thing contains the same set of instructions responsible for coding the blueprint of that entire organism: DNA. However, in most cases, it is easy to see that each cell does not look the same and is highly specialised – we wouldn’t, for example, want eyes growing from the tips of our toes. It is a different molecule, RNA, which serves as a messenger between DNA instructions and protein products that give cells their characteristics. We have been able to read these sequences from ground-up tissue for a long time, but to sequence the RNA of individual cells has provided an unprecedented level of resolution.

This was first done in 2009, by Fuchou Tang and colleagues. They wanted to develop a sequencing technique using RNA harvested from a single cell, because traditional RNA-sequencing approaches require large amounts of RNA that are often impractical to obtain. They harvested RNA from a single mouse embryo cell and sequenced it. From there, they needed to prove that their technique was better than sequencing tissue in bulk. They compared it to experiments run on similar samples and demonstrated that theirs detected more genes and RNA variants, as well as changes caused by alterations in gene signalling pathways. This was also the first study to demonstrate that hundreds of genes express multiple RNA variants in the same cell at the same time. Their results show the extreme complexity of cells which has never before been conceived. Thus, their endeavour was a success but, as any reputable scientist does, they pointed out their limitations associated with RNA harvesting and RNA strand directional information.

All this is said in the context of this paper being the first of its kind 14 years ago. These limitations have since been addressed and remarkable advances in single-cell sequencing technologies have been made that will truly show you the marvel of what makes up life on Earth. I implore you to dive in!

Reference

Paper: Tang, F., Barbacioru, C., Wang, Y. et al. mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods 6, 377–382 (2009). https://doi.org/10.1038/nmeth.1315