西亚试剂：PDGFRβ Expression and Function in Fibroblasts Derived from

PDGFRβ Expression and Function in Fibroblasts Derived from Pluripotent Cells is Linked to DNA Demethylation

Kyle J. Hewitt, Yulia Shamis, Elana Knight, Avi Smith, Anna Maione, Addy Alt-Holland, Steven D. Sheridan, Stephen J. Haggarty and Jonathan A. Garlick

Platelet-derived growth factor receptor-beta (PDGFRβ) is required for the development of mesenchymal cell types, and plays a diverse role in the function of fibroblasts in tissue homeostasis and regeneration. In this study, we characterized the expression of PDGFRβ in fibroblasts derived from human embryonic stem cells and induced pluripotent stem cells, and showed that this expression is important for cellular functions including migration and extracellular matrix production and assembly in 3D self-assembled tissues. To determine potential regulatory regions predictive of expression of PDGFRβ following differentiation from ESC and iPSC, we analyzed the DNA methylation status of a region of the PDGFRβ promoter containing multiple CpG sites before and after differentiation. We demonstrated that this promoter region is extensively demethylated following differentiation, and represents a developmentally-regulated, differentially-methylated region linked to PDGFRβ expression. Understanding the epigenetic regulation of genes such as PDGFRβ, and identifying sites of active DNA demethylation, is essential for future applications of pluripotent stem cell-derived fibroblasts for regenerative medicine.

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