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.

Polyvinylidene fluoride (PVDF) is a stable and biocompatible material that has been broadly used in biomedical applications. Due to its piezoelectric property, the electrospun nanofiber of PVDF has been used to culture electroactive cells, such as osteocytes and cardiomyocytes. Here, taking advantage of the piezoelectric property of PVDF, we have fabricated a PVDF nanofiber scaffolds using an electrospinning technique for differentiating human embryonic stem cells (hESCs) into neural precursors (NPs). Surface coating with a peptide derived from vitronectin enables hESCs to firmly adhere onto the nanofiber scaffolds and differentiate into NPs under dual-SMAD inhibition. Our nanofiber scaffolds supported the differentiation of hESCs into SOX1-positive NPs more significantly than Matrigel. The NPs generated on the nanofiber scaffolds could give rise to neurons, astrocytes, and oligodendrocyte precursors. Furthermore, comparative transcriptome analysis revealed the variable expressions of 27 genes in the nanofiber scaffold groups, several of which are highly related to the biological processes required for neural differentiation. These results suggest that a PVDF nanofiber scaffold coated with a vitronectin peptide can serve as a highly efficient and defined culture platform for the neural differentiation of hESCs.

Parkinson’s disease (PD) is a movement disorder caused by progressive degeneration of the midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNc). Despite intense research efforts over the past decades, the etiology of PD remains largely unknown. Here, we discovered the involvement of trophoblast glycoprotein (Tpbg) in the development of PD-like phenotypes in mice. Tpbg expression was detected in the ventral midbrain during embryonic development and in mDA neurons in adulthood. Genetic ablation of Tpbg resulted in mild degeneration of mDA neurons in aged mice (12–14 months) with behavioral deficits reminiscent of PD symptoms. Through in silico analysis, we predicted potential TPBG-interacting partners whose functions were relevant to PD pathogenesis; this result was substantiated by transcriptomic analysis of the SNc of aged Tpbg knockout mice. These findings suggest that Tpbg is a new candidate gene associated with PD and provide a new insight into PD pathogenesis.

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