Human umbilical cord-derived mesenchymal stem cells (hUC-MSC) are one type of mesenchymal stem cells and more primitive than other MSCs. In this study, we identify novel genes and signal-activating proteins involved in the neural differentiation of hUC-MSCs induced by Low Intensity Sub-Sonic Vibration (LISSV). RNA sequencing assay was used to find genes involved in the differentiation process by LISSV. The changes of hUC-MSCs caused by LISSV were confirmed by Plexin A4 (PLXNA4) overexpression, and gene knockdown through small interfering RNA experiments. The six genes were increased among genes related to neurons and the nervous system. One of them, the PLXNA4 gene, is known to play a role as a guide for axons in the development of the nervous system. When PLXNA4 protein was added, neuron-related genes were increased. In the PLXNA4 gene knockdown experiment, the expression of neuron-related genes was not changed by LISSV exposure. The PLXNA4 gene is activated by sema family ligands. The Sema3A gene was increased by LISSV, and its downstream signaling molecule, FYN, was also activated. We suggest that the PLXNA4 gene plays an important role in hUC-MSC neuronal differentiation through exposure to LISSV. The differentiation process depends on semaphorin 3A-plexin A4 dependent FYN activation in hUC-MSCs.