Satellite glial contact enhances differentiation and maturation of human iPSC-derived sensory neurons

Sensory neurons generated from induced pluripotent stem cells (idSNs) are used to model human peripheral neuropathies; however, current differentiation protocols produce cells with an embryonic phenotype. Peripheral glia contact sensory neurons early in development and contribute to formation of the canonical pseudounipolar morphology, but these signals are not encompassed in current idSN differentiation protocols. Here, we show that terminal differentiation of idSNs in coculture with rat dorsal root ganglion (rDRG) satellite glia and glial precursors (rSG) advances differentiation and maturation. Cocultured idSNs develop pseudounipolar morphology through contact with rSG. In addition to morphological changes, idSNs terminally differentiated in coculture exhibit enhanced action potential firing, more mature gene expression, and increased susceptibility to paclitaxel-induced axonal degeneration. Thus, idSNs differentiated in coculture with rSG provide a better model for investigating human peripheral neuropathies.