IntroductionNeuroplasticity is evoked by extracellular signals that bind receptors in the plasma membrane to induce signal transduction that results in polarized actions in the neuronal plasma membrane. Membrane/lipid rafts (MLR) and cholesterol binding protein caveolin‐1 (Cav‐1) provide a signaling membrane platform that tethers and regulates cytoskeletal components necessary for proper dendritic growth, maintenance and neuroplasticity. Our lab has demonstrated in rodents primary neurons that overexpression of neuronal cav‐1 enhances pro‐growth/pro‐survival signaling, and improves dendritic growth and arborization. We utilized neurons derived from human induced pluripotent stem cells (iPSCs) to ask whether Cav‐1 controls similar signaling and functions in human neurons as it does in rodent neurons. We overexpressed Cav‐1 driven by the neuronal specific synapsin promoter (SynCav1) and evaluated changes in dendritic morphology after the differentiation process.MethodsiPSC derived neuronal stem cells (NSCs) were cultured in DMEM/F12+Gluamax media with N‐2 supplement, B‐27 supplement, Pen/Strep, and basic Fibroblast Growth Factor (bFGF). Neuronal differentiation was started by bFGF withdrawal from media. NSCs were transfected with either SynCav1 or SynGFP as control when differentiation was started. Cells were fixed 3 weeks after differentiation and stained for Cav‐1, the dendritic marker microtubule‐associated protein 2 (MAP2), and the axonal marker neurofilament (SMI‐31). Dendritic length, branching (arborization), area, and volume were measured by Autoneuron (MBF Bioscience), a tracing algorithm that measures 3D image volume stacks. Cells were also collected and homogenized to measure Cav‐1 levels via western blots.ResultsWestern blots showed that Cav‐1 was increased in the cells transfected with SynCav‐1 compared to SynGFP 3 weeks after differentiation. Compared with SynGFP, SynCav1 transfection significantly enhanced dendritic length (p=0.002), branching points/arborization (p=0.0004), dendrite area (p=0.003), and dendrite volume (p=0.009)ConclusionNeuron‐targeted expression of Cav‐1 significantly enhanced dendritic growth of human iPSC‐derived neurons suggesting the presence of efficient Cav‐1 dependent signaling in these cells.