Histamine-induced Ca²⁺signalling is mediated by TRPM4 channels in human adipose-derived stem cells

Intracellular Ca²⁺oscillations are frequently observed during stem cell differentiation, and there is evidence that it may control adipogenesis. The transient receptor potential melastatin 4 channel (TRPM4) is a key regulator of Ca²⁺signals in excitable and non-excitable cells. However, its role in human adiposederived stem cells (hASCs), in particular during adipogenesis, is unknown. We have investigated TRPM4 in hASCs and examined its impact on histamine-induced Ca²⁺signalling and adipogenesis. Using reverse transcription (RT)-PCR, we have identified TRPM4 gene expression in hASCs and human adipose tissue. Electrophysiological recordings revealed currents with the characteristics of those reported for the channel. Furthermore, molecular suppression of TRPM4 with shRNA diminished the Ca²⁺signals generated by histamine stimulation, mainly via histamine receptor 1 (H1) receptors. The increases in intracellular Ca²⁺were due to influx via voltage-dependent Ca²⁺channels (VDCCs) of the L-type (Cav1.2) and release from the endoplasmic reticulum. Inhibition of TRPM4by shRNAinhibited adipogenesis as indicated by the reduction in lipid droplet accumulation and adipocyte gene expression. These results suggest that TRPM4 is an important regulator of Ca²⁺signals generated by histamine in hASCs and is required for adipogenesis.