Summary
The human body is made up of many different types of cells, such as blood cells, skin cells, and neurons in the brain.
Figure 1: Some examples of human cell types. Created with BioRender.com.
What distinguishes these different ‘cell types’ and what dictates their different characteristics, are the genes they express or ‘turn on’ 1.
Using modern genomics and a technology known as single-cell RNA-sequencing (scRNA-seq)2, we can identify exactly which genes (out of all 20,000+ genes in the genome) that are expressed in individual cells of a tissue/organism. This allows us to profile the cells of say, a cancer tumour, or a developing mouse embryo, and characterise it’s cellular makeup at extremely high resolution.
Figure 2: Click to explore in 3D. scRNA-seq data is often visualised using a UMAP plot where each point represents an individual cell, and the distances between cells reflect their similarity in gene expression. In this 3D UMAP, each cell was isolated from rabbit embryos during development3. Using gene expression alone, different types of cells are identifiable as clusters (coloured). We can also see developmental trajectories, which represent gene expression changes as cells transition from one cell state to another (differentiate). E.g. erythroid cells (in red) develop from megakaryocyte–erythroid progenitors (MEPs).
Over the last 5 years, single-cell RNA-sequencing has been applied to study how genes are expressed across many different species spanning the tree of life. As a result, we are now able perform deep comparisons between cells and their molecular properties across a range of organisms. These similarities and differences at the level of individual cells can help us reconstruct the evolution of different cell types. It can also help us to identify aspects of molecular biology which are conserved across different species, which may help us to translate findings from model organisms to humans.
During my PhD, I have explored both evolutionary and translational applications of cross-species single-cell analysis, through projects studying early rabbit development and investigating the evolution of the vertebrate brain.