The Genetic Program of Pancreatic [Beta]-Cell Replication In Vivo

The molecular program underlying infrequent replication of pancreatic ...-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating ...-cells and determined their transcriptome. Replicating ...-cells upregulate hundreds of proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved in ...-cell functions, namely, glucose sensing and insulin secretion, were repressed. Further studies using single-molecule RNA in situ hybridization revealed that in fact, replicating ...-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in ...-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 ...-cells in vivo. (ProQuest: ... denotes formulae/symbols omitted.)