Single-cell sequencing at Earlham Institute

Multicellular organisms like plants, mice and humans contain many billions – often trillions - of cells, all of which originate from a single cell, or zygote, after fertilisation. As the organism develops from the zygote, cells make changes to their gene expression profiles, a process termed differentiation, allowing them to fulfil diverse and unique tasks throughout the organism.

Next generation sequencing (NGS) typically analyses pools of thousands, or even millions of single cells – and much of the detail and complexity of the cellular populations within these pools is lost. Single cell genomics approaches allow us to apply NGS technologies to the tiny amounts of DNA (genome) and RNA (transcriptome) that can be found in a single cell.

Currently, most single cell genomics work focuses on the transcriptome – to study the diversity of cell types arising during development and differentiation of the organism, as the cells make changes to the genes they express. By sequencing the transcriptomes of many individual cells, we can explore how many different cell types there are in an organism. We can also start to learn something about the function of those different cell types by looking at the kinds of genes they express.

From sequencing the genomes of single cells, we can learn about the mutations that the cell may have gained during development – this technology is particularly useful in teasing apart how cancer cells have ‘evolved’ within a patient. We can also use single cell sequencing approaches to study diversity in the epigenomes of single cells, by examining DNA methylation.

At EI, we are developing single cell approaches to apply across a wide range of species – from microbial populations to plants and mammals. One of the main technical focuses of single cell our single-cell genomics research is the integration of data types, so in parallel, we can understand gene expression and regulation within a single cell.