Remodeling of calcium signaling and store operated calcium entry as a consequence of human neural progenitor cell differentiation

The differentiation of neural progenitor cells into glial and neuronal lineages is a fundamental process in neurodevelopment. This complex process is tightly regulated by several signaling pathways, including calcium signaling. Calcium signaling not only regulates neural progenitor proliferation and survival but also regulates gene expression changes that drive the differentiation process and cell fate. One calcium signaling pathway that has been associated with neural progenitor cells proliferation and differentiation is store-operated calcium entry (SOCE), mediated by STIM and ORAI proteins. Using human neural progenitor ReNcell VM model expressing a genetically encoded calcium indicator and high content imaging methods, calcium signaling changes associated with neuronal differentiation were assessed. Differentiated cells exhibited increased spontaneous Ca²⁺ oscillation and ligand-activated oscillations. Neural progenitor cell differentiation was associated with a shift away from canonical SOCE, with increased expression in ORAI3, which was also identified as a potential regulator of differentiation in this model.