Spliceostatin A treatment inhibits mitotic clonal expansion and adipogenesis

Abstract

Adipogenesis is a differentiation process from mesenchymal stem cells to adipocytes. It has been reported that adipogenesis is regulated by a highly orchestrated transcriptional cascade. However, the effects of modulation of mRNA splicing on adipogenesis remain unknown. To investigate these effects, 3T3-L1 preadipocyte were treated with the potent splicing inhibitor spliceostatin A, which revealed that splicing inhibition suppressed adipogenesis. In addition, treatment of 3T3-L1 cells with spliceostatin A during the early phase of adipogenesis was sufficient to inhibit adipogenesis. In the early phase of adipogenesis, the cells re-entered the cell cycle, which is referred to as mitotic clonal expansion. As mitotic clonal expansion is required for adipogenesis, it was assumed that splicing inhibition would suppress mitotic clonal expansion, and consequently inhibit adipogenesis. As expected, spliceostatin A treatment caused G1 phase arrest and inhibited cell proliferation, i.e., inhibition of mitotic clonal expansion. These results suggest that splicing activity is required for mitotic clonal expansion and adipogenesis.