Single Cell Transcriptomic Analysis of Pancreatic β Cell Development and Differentiation from Pluripotent Stem Cells

Abstract

Single cell genomics is a powerful tool to study cellular heterogeneity and discover novel cell types. Recent studies used single cell RNA sequencing (scRNA-seq) to analyze the transcriptomes of individual pancreatic islet cells. Islets are a complex mixture of endocrine cells and therefore represent an ideal tissue type for single cell transcriptomic analysis. Adult human islets consist of five known endocrine cell types (α, β, δ, γ, ε) and multiple less welldefined non-endocrine cells. In this review, we discuss the scRNA-seq studies performed on human fetal, adult, diseased and pluripotent stem cell-derived islets in recent years. Since 2015, ~30,000 adult human islet cells have been analyzed using several scRNA-seq technologies. Studies provide a complete catalogue of all islet cell types and subtypes found throughout human development from fetus to adulthood. Islets from patients with Type 2 diabetes have also been analyzed with scRNA-seq unraveling multiple mechanisms of islet dysfunction. Advances in stem cell differentiation protocols and cell therapy manufacturing are bringing stem cell-derived islets (SC-Islets) closer to clinical trials. In 2018, more than 60,000 SC-Islet cells were analyzed using scRNA-seq technologies. Lessons learned include SC-Islet cell populations, lineage trajectories and comparative analyses to adult human islet cell transcriptomes. Studies have also identified and characterized the non-islet, off-target cell populations revealing potential strategies for their elimination.