Tcf19 and Regulation of Beta Cell Proliferation

Tcf19 is a largely uncharacterized transcription factor that is expressed during cell division, beginning at G1/S phase. In a mouse model of obesity-associated diabetes, we identified tcf19 within a group of cell cycle genes whose expression correlates with adaptive islet proliferation. In confirmation of these microarray data, we observed 3.3-fold upregulation of tcf19 mRNA in islets from obese non-diabetic C57Bl/6J (B6) mice vs. lean (n=5, p=0.01). This obesity-driven upregulation was not observed in islets from the diabetic BTBR  strain. Tcf19 is most highly expressed in islet, which is an unusual pattern of expression for a cell cycle regulator since numerous tissues have higher basal proliferation rates, and suggests that tcf19 may play a more specific role in cell cycle regulation in the islet. The role of tcf19 in beta cell growth was then examined. After siRNA-mediated knockdown of tcf19 in INS-1 cells, a significant reduction in the number of viable cells was found. Proliferation was directly measured by 3H-thymidine incorporation and a 40% reduction was found with tcf19 knockdown (n=3, p=0.012). In summary, tcf19 is necessary for beta cell proliferation and may play a role in obesity-driven proliferation in mouse islets.