A Novel Vitronectin Peptide Facilitates Differentiation of Oligodendrocytes from Human Pluripotent Stem Cells (Synthetic ECM for Oligodendrocyte Differentiation)

SIMPLE SUMMARY: Oligodendrocyte (OD) is a cell type of great interest in the regenerative medicine for several neurological diseases. This study provides a new defined coating material for the differentiation of ODs from human pluripotent stem cells. A new peptide named VNP2, designed by in silico simulation, can be readily produced in a large amount and stably immobilized on the bottom of culture vessel. Upon using for differentiation of ODs, VNP2 promoted the differentiation efficiency more than the conventional coating materials did. Furthermore, transcriptomic analysis revealed molecular clues for the differentiation promoting activity of VNP2. Therefore, this peptide may be used as a favored coating material for the culture and differentiation of ODs. ABSTRACT: Differentiation of oligodendrocytes (ODs) presents a challenge in regenerative medicine due to their role in various neurological diseases associated with dysmyelination and demyelination. Here, we designed a peptide derived from vitronectin (VN) using in silico docking simulation and examined its use as a synthetic substrate to support the differentiation of ODs derived from human pluripotent stem cells. The designed peptide, named VNP2, promoted OD differentiation induced by the overexpression of SOX10 in OD precursor cells compared with Matrigel and full-length VN. ODs differentiated on VNP2 exhibited greater contact with axon-mimicking nanofibers than those differentiated on Matrigel. Transcriptomic analysis revealed that the genes associated with morphogenesis, cytoskeleton remodeling, and OD differentiation were upregulated in cells grown on VNP2 compared with cells grown on Matrigel. This new synthetic VN-derived peptide can be used to develop a culture environment for efficient OD differentiation.