Resolving single cells by RNA sequencing

Scientists are now trying to dissect this heterogeneity in host-salmonella interactions by investigating the behavior of single cells at an unprecedented resolution. "This is very challenging to study as bacterial numbers are minute during different stages of salmonella infection. So, we need sensitive tools to probe them," said Prof. Roi Avraham, Principal Investigator in the Department of Immunology and Regenerative Biology at the Weizmann Institute of Science, during a session at ASM Microbe 2022. One technique that is sensitive enough to dissect these complex interactions is RNA sequencing (RNA-seq). Traditional bulk RNA-seq reveals the average transcriptome—expression levels of different genes in cells—by quantifying messenger RNA, or mRNA, in a given sample.

In the past decade, scientists have unleashed the potential of single-cell RNA sequencing (scRNA-seq) to investigate host-microbe interactions. scRNA-seq provides information about the transcriptome in single cells, offering a high spatiotemporal view of the infection landscape. An analogy that is often mentioned in reference to single-cell techniques is that of a fruit smoothie—while bulk measurements can provide information about the overall characteristics of the fruit smoothie, single-cell technologies provide information about individual pieces of strawberry, banana, apple and so forth.