Small molecules induces dorsal root ganglion satellite glial cells to differentiate into sensory neuron-like cells

Abstract

The inability of damaged neurons to regenerate poses a significant challenge in the repair of peripheral nerve injuries. Exogenous cell therapies, such as those involving neural stem cells or induced pluripotent stem cells, are limited by immune rejection and ethical concerns. Somatic cells offer a promising alternative, as they can be reprogrammed and differentiated into neuron-like cells, thereby promoting nerve repair. Satellite glial cells (SGCs) within the dorsal root ganglion (DRG) have the capacity to differentiate into multiple cell types. In this study, chemical small molecules were used to replace transcription factors and induce DRG-derived SGCs to differentiate into sensory neuron-like cells. Subsequently, cell viability, morphology, and functionality were evaluated using CCK-8 assays, immunocytochemistry, qRT-PCR, ELISA, confocal calcium imaging, and ultra-high-resolution transmission electron microscopy. The induced cells expressed key sensory neuron markers, including CGRP, PSD95, Synapsin, PRPH, TrkA, TrkB, TrkC, Ret, AnkyrinG, and Brn3a. Moreover, they displayed gene expression patterns associated with sensory neuron development, such as those of Avil, TrkA, Brn3a, Isl1, Runx3, and Shox2. Importantly, these cells exhibited calcium transients in response to KCl, BayK, and capsaicin stimulation. Capsaicin treatment also resulted in increased levels of CGRP and substance P, suggesting that the induced cells exhibit characteristics of mature neurons, including synaptic structures, functional calcium channels, and active signaling pathways. Our findings demonstrate that DRG-derived SGCs can be chemically induced to differentiate into sensory neuron-like cells, representing a novel approach for neuronal cell fate acquisition and a potential cell source for peripheral nerve repair.