Genome-wide RNA-sequencing of human islets 48 hour after transduction with adenoviruses expressing either GFP (control), or histone chaperone ASF1B.

Comparison of gene expression in pancreatic islets of BTBR-ob/ob mouse model of obesity-induced type 2 diabetes, and in non-diabetic control mice, B6-ob/ob identified Asf1b as an important gene candidate predictive of diabetic outcome. Asf1B expression was suppressed in response to age in both B6 and BTBR islets, induced by obesity only in B6 islets. This is consistent with other studies reporting a decline in ?-cell proliferation with age. Asf1b also strongly correlated (R ~ 0.98) with cellular proliferation marker Mki67. Overexpression of Asf1B induced ß-cell proliferation in human islets. We show that many genes involved in regulation of cell cycle or programmed cell death are differentially regulated by Asf1B overexpression. Overall design: Ten different human islet preparations were obtained from 9 individual donors (from IIDP program). Each preparation contained approximately 20,000 islet equivalent units. Each islet preparation was separated into two portions for adenoviral transduction to overexpress GFP (control) or ASF1B genes.