Modeling pancreatic beta cell senescence by induction of DNA double-strand breaks

Pancreatic beta cell senescence occurs during the development of Type 1 Diabetes. To model the transcriptional responses of islet cells to DNA damage, we previously developed a human islet culture model in which the DNA damage response and senescence can be induced via double strand-breaks with the agent bleomycin. Here, we report the transcriptome-wide changes in human pancreatic islet cells following bleomycin exposure. Overall design: Human donor islets isolated from a 44 year old normoglycemic female by Scharp-Lacy and distributed by the Integrated Islet Distribution Program (RRID:SAMN13186657) and from a 50 year old normoglycemic female by Alberta Diabetes Institute (RRID:SAMN26419385) were rested 24 h and then treated with vehicle (DMSO) or 50 uM bleomycin for 48 h. Islets from each donor were treated with Veh or Bleo in n=3 biological replicates (wells of islets). Following this, the islets were transferred to fresh drug free media and cultured an additional 4 days before harvest and RNA extraction. Approximately 1 ug of total RNA was submitted to LC Sciences for total RNA-seq on Illumina NovaSeq 6000 platform.