Single-cell insights into transcriptomic diversity in immunity

Our body is composed of a diverse set of cells that together perform numerous functions in a highly coordinated manner, allowing a timely response to external cues and to inter-cellular signals. Emerging single-cell technologies enable investigation of these intricate processes at an unprecedented level. Here, we discuss recent work on cellular differentiation and heterogeneity, and describe novel experimental and computational tools that enable this research. As an example of cellular differentiation, we focus on T cell development in response to diverse infections and in immune pathologies. We then describe how single-cell studies have contributed to our understanding of transcriptional variability in innate immune response, and how this variability might be important in achieving a balanced immune response. Future single-cell studies will likely include spatial analyses and lineage tracing strategies, holding great potential to further our understanding of cell behaviour in steady-state and pathological conditions.This project was supported by ERC grants (ThDEFINE and ThSWITCH) and an EU FET-OPEN grant (MRG-GRAMMAR). T.H was supported by a Human Frontier Science Program Long-Term Fellowship (LT000229/2013) and by an EMBO Long-Term fellowship (ALTF 280-2014). R.J.M. was supported by a PhD Fellowship (SFRH/BD/51950/2012) from Fundação para a Ciência e Tecnologia, Portugal.