Mapping the splicing landscape of the human immune system

Most human genes code for more than one transcript. Different ratios of transcripts of the same gene can be found in different cell types or states, indicating differential use of transcription start sites or differential splicing. Such differential transcript use (DTUs) events provide an additional layer of regulation and protein diversity. With the exceptions of PTPRC and CIITA, there are very few reported cases of DTU events in the immune system. To rigorously map DTUs between different human immune cell types, we leveraged four publicly available RNA sequencing datasets. We identified 282 DTU events between five human healthy immune cell types that appear in at least two datasets. The patterns of the DTU events were mostly cell-type-specific or lineage-specific, in the context of the five cell types tested. DTUs correlated with the expression pattern of potential regulators, namely, splicing factors and transcription factors. Of the several immune related conditions studied, only sepsis affected the splicing of more than a few genes and only in innate immune cells. Taken together, we map the DTUs landscape in human peripheral blood immune cell types, and present hundreds of genes whose transcript use changes between cell types or upon activation.

Automated summary

Most human genes code for multiple transcripts, which can have different ratios in different cell types or states. These differential transcript use (DTUs) events provide an additional layer of regulation and protein diversity. By analyzing publicly available RNA sequencing datasets, we identified 282 DTU events in five human healthy immune cell types, with patterns mostly specific to cell types or lineages and correlated with the expression of potential regulators. Only sepsis affected gene splicing in a few genes and only in innate immune cells. This study maps the landscape of DTUs in human immune cells and provides insights into transcript use changes.