The role of human NME1 in neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells

Mesenchymal stem cells (MSCs), also known as multipotent stromal cells, has a possibility to differentiate into the neurallike cells as well as other type of cells such as osteoblast and adipocyte. Moreover, ganglioside, a sialic acidcontaining glycosphingolipids, plays a significantly critical role in the neuronal differentiation of MSCs. Meanwhile, macrophages (MPs), which secrets many type of proteins including human nucleoside diphosphate kinase A (hNME1) in the body, has been considered to involve closely in the neuronal differentiation of MSCs. Herein, we investigated and analyzed the correlation between the inhibitory effect of MP secretomes and the expression of ganglioside in the neuronal differentiation. Our results show that hNME1 strongly and specifically binds pST8SIA1, which is a ganglioside GD3 synthase, suggesting that hNME1 is a key factor in the inhibitory. Consequently, we produced nanobodies (NBs) named NB-hNME1 that effectively blocked the binding of hNME1, and thereby recovered the expression of ganglioside GD3 and the neuronal differentiation of MSCs.