Single-Cell RNA-Seq of the Pancreatic Islets--a Promise Not yet Fulfilled?

In the past 3 years, we have seen a flurry of publications on single-cell RNA sequencing (RNA-seq) analyses of pancreatic islets from mouse and human. This technology holds the promise to refine cell-type signatures and discover cellular heterogeneity among the canonical endocrine cell types such as the glucagon-producing α and insulin-producing β cells, going as far as suggesting new subtypes. In addition, single-cell RNA-seq has the ability to characterize rare endocrine cell types that are not captured by prior bulk analysis. With transcriptomics data from individual endocrine cells, cellular states can be profiled both along developmental processes and during the emergence of metabolic diseases. However, the promises of this new technology have not yet been met in full. While the methodology for the first time enabled the transcriptional definition of rare endocrine cell types such as ghrelin-producing ɛ cells, some of the conclusions regarding cell-type-specific gene expression changes in type 2 diabetes might need to be revisited once larger sample sizes become available. Data generation and analysis are continuously improving single-cell RNA-seq approaches and are helping us to understand the (mal)adaptations of the islet cells during development, metabolic challenge, and disease.