Vascular smooth muscle cell derived from iPS cell of Moyamoya disease - Comparative characterization with endothelial cell transcriptome

Transcriptome analysis of vascular smooth muscle cells differentiated from iPS-derived neural crest stem cells in Moyamoya disease Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by steno-occlusive changes in the cerebral arteries at the base of the brain with unknown etiology, although histopathological features have demonstrated as fibrocellular thickening of the intima and medial thinning on the steno-occlusive arteries. However, the pathophysiology of proliferating cells in the thickened intima is still obscure. Furthermore, biological features of the vascular smooth muscle cells are unclear in MMD. Here, we aimed to analyze whole genome gene expression profile in VSMC using induced pluripotent stem (iPS) cell line. We generated iPS cell line from the blood of MMD with RNF213 R4810K risk allele (rs112735431) or healthy control without the risk allele. VSMCs were differentiated from iPS-derived neural crest stem cells. As a result, we successfully established cranio-cervical region specific VSMC confirmed by immunocytochemistry. Biological cellular features, including cellular proliferation, migration, and contraction ability were similar in VSMCs between MMD and control. Genome-wide gene expression analysis showed similar transcriptome profile in the VSMCs between MMD and control. Differential gene expression analysis in MMD-VSMC revealed 6 differentially expressed genes (4 upregulated, 2 down regulated in MMD), including decorin (DCN, upregulated in MMD), playing an inhibitory role in angiogenesis. In conclusion, VSMCs are not impaired in cellular function with similar transcriptome profile in MMD compared to healthy control. Since many previous studies have shown impaired EC features in MMD, our study suggests EC may play more role in the vascular pathogenesis in MMD rather than VSMC. We analyzed vascular smooth muscle cells (VSMC) in three patients with Moyamoya disease and three healthy control volunteers using the Affymetrix GeneChip HG-U133 Plus 2 platform. Array data was processed by Affymetrix Exon Array Computational Tool. VSMCs were differentiated from iPS-derived neural crest stem cells derived from peripheral blood mononuclear cells. No technical replicates were performed.