Single-Cell RNA-seq Reveals a Subpopulation of Cells Underlying β Cell Expansion in the Postnatal Islets

Abstract

Pancreatic {beta} cells undergo significant expansion and maturation during human and rodent postnatal development. Here, we used single-cell RNA-seq to characterize gene expression patterns at various stages of mouse islet cell development and uncovered a population of cells that is most abundant during the early postnatal period. This cell population lacks expression of FLTP and expresses PDGF receptors. Each of these conditions have previously been associated with proliferative capacity in {beta} cells suggesting that we have identified the proliferative competent of {beta} cell mass expansion. The subpopulation co-express many endocrine lineage-specific genes and exhibits a downregulation of genes associated with mitochondrial oxidative phosphorylation and global protein synthesis. It has upregulated activity of genes in the Wnt, Hippo, PDGF, and Notch pathways and has a significantly higher proliferation potential than the more mature {beta} population. We show that activity of the Notch pathway is required in postnatal {beta} cell expansion where it serves to maintain an undifferentiated endocrine state in the polyhormonal cell population. Collectively, our study identifies a proliferative, progenitor-like cell subpopulation in the postnatal islet as the source of postnatal {beta} cell expansion.