Gene Signature of Proliferating Human Pancreatic α Cells

• Published in: Endocrinology (Philadelphia) Vol. 159; no. 9; pp. 3177 - 3186
• Main Authors: Dominguez Gutierrez, Giselle, Xin, Yurong, Okamoto, Haruka, Kim, Jinrang, Lee, Ann-Hwee, Ni, Min, Adler, Christina, Yancopoulos, George D, Murphy, Andrew J, Gromada, Jesper
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.09.2018
• Subjects: Beta cells; Cell cycle; Cell differentiation; Cell division; Cell proliferation; Endocrinology; Gene expression; Gene regulation; Gene sequencing; Genes; Inhibitors; Insulin; Pancreas; Ribonucleic acid; RNA; Subpopulations
• ISSN: 1945-7170; 0013-7227; 1945-7170
• DOI: 10.1210/en.2018-00469

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