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Oscillatory Expression of Stem Cell-associated Genes in Pattern Forming Calcifying Vascular Cells

Abstract

Multipotent CVCs are used as models for atherosclerotic lesion cells due to their capacity to calcify, but the molecular or cellular mechanisms involved are not completely known. Recent work has reported that stem cell-associated factors show patterned responses in vertebrate segmentation and other cells in embryonic development, suggesting that oscillatory expression is a general feature for many cellular events. In this study, we explored connections between the expression of multipotency markers and pattern formations in CVCs. Control CVCs, BMP-4 treated CVCs, and MGP depleted CVCs were cultured separately in a two-week time period, and the expression of Sox2, Nanog, Klf4, and Oct-3/4 were analyzed with real-time PCR. Furthermore, the relationship between the osteogenic potential of CVC and these genes was briefly explored. Our results suggest that CVCs may exhibit oscillatory genetic expression as they form patterns, and that BMP inhibition by MGP is essential to maintaining oscillations and pattern formations.

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