Lamin A/C mutation associated with lipodystrophy influences adipogenic differentiation of stem cells through interaction with Notch signaling

Lamin A/C is involved in many cellular functions due to its ability to bind chromatin and transcription factors and affect their properties. Mutations of LMNA gene encoding lamin A/C affect differentiation capacity of stem cells. However, signaling pathways involved in interaction with lamins in cellular differentiation remain unclear. Lipodystrophy associated with LMNA mutation R482L causes loss of fat tissue. In this study we investigated the role of LMNA mutation R482L in modulating Notch signaling activity in adipogenic differentiation of mesenchymal stem cells. Notch was activated using lentiviral Notch intracellular domain. Activation of Notch was estimated by expression of Notch-responsive genes by qPCR and by activation of luciferase CSL-reporter construct. Effect of LMNA mutation on Notch activation and adipogenic differentiation was analyzed in cells bearing lentiviral LMNA WT or LMNA R482L. We show that LMNA R482L contributes to down regulation of Notch activation in undifferentiated and differ...