RT Journal Article SR Electronic T1 The Genetic Program of Pancreatic β-Cell Replication In Vivo JF Diabetes JO Diabetes FD American Diabetes Association SP 2081 OP 2093 DO 10.2337/db16-0003 VO 65 IS 7 A1 Klochendler, Agnes A1 Caspi, Inbal A1 Corem, Noa A1 Moran, Maya A1 Friedlich, Oriel A1 Elgavish, Sharona A1 Nevo, Yuval A1 Helman, Aharon A1 Glaser, Benjamin A1 Eden, Amir A1 Itzkovitz, Shalev A1 Dor, Yuval YR 2016 UL http://diabetes.diabetesjournals.org/content/65/7/2081.abstract AB The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating β-cells and determined their transcriptome. Replicating β-cells upregulate hundreds of proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved in β-cell functions, namely, glucose sensing and insulin secretion, were repressed. Further studies using single-molecule RNA in situ hybridization revealed that in fact, replicating β-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in β-cell function. These data suggest that the quiescence-proliferation transition involves global amplification of gene expression, except for a subset of tissue-specific genes, which are “left behind” and whose relative mRNA amount decreases. Our work provides a unique resource for the study of replicating β-cells in vivo.