Gene signature of proliferating human pancreatic a cells

Abstract

Pancreatic a cells proliferate at a low rate, and little is known about the control of this process. Here we report the characterization of human a cells by large-scale, single-cell RNA sequencing coupled with pseudotime ordering. We identified two large subpopulations and a smaller cluster of proliferating a cells with increased expression of genes involved in cell-cycle regulation. The proliferating a cells were differentiated, had normal levels of GCG expression, and showed no signs of cellular stress. Proliferating a cells were detected in both the G1S and G2M phases of the cell cycle. Human a cells proliferate at a fivefold higher rate than human b cells and express lower levels of the cell-cycle inhibitors CDKN1A and CDKN1C. Collectively, this study provides the gene signatures of human a cells and the genes involved in their cell division. The lower expression of two cell-cycle inhibitors in human a cells could account for their higher rate of proliferation compared with their insulin-producing counterparts.