Gene Signature of Proliferating Human Pancreatic α-Cells.

Pancreatic alpha cells proliferate at a low rate, and little is known about the control of this process. Here we report the characterization of human alpha 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 alpha cells were detected in both the G1S and G2M phases of the cell cycle. Human alpha cells proliferate at a fivefold higher rate than human beta cells and express lower levels of the cell-cycle inhibitors CDKN1A and CDKN1C. Collectively, this study provides the gene signatures of human alpha cells and the genes involved in their cell division. The lower expression of two cell-cycle inhibitors in human alpha cells could account for their higher rate of proliferation compared with their insulin-producing counterparts.