From words to complete phrases: insight into single-cell isoforms using short and long reads

The profiling of gene expression patterns to glean biological insights from single cells has become commonplace over the last few years. However, this approach overlooks the transcript contents that can differ between individual cells and cell populations. In this review, we describe early work in the field of single-cell short-read sequencing as well as full-length isoforms from single cells. We then describe recent work in single-cell long-read sequencing wherein some transcript elements have been observed to work in tandem. Based on earlier work in bulk tissue, we motivate the study of combination patterns of other RNA variables. Given that we are still blind to some aspects of isoform biology, we suggest possible future avenues such as CRISPR screens which can further illuminate the function of RNA variables in distinct cell populations.