title: PDGFRβ expression and function in fibroblasts derived from pluripotent cells is linked to DNA demethylation.
abstract: 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 (ESCs) and induced pluripotent stem cells (iPSCs), and showed that this expression is important for cellular functions such as migration, extracellular matrix production and assembly in 3D self-assembled tissues. To determine potential regulatory regions predictive of expression of PDGFRβ following differentiation from ESCs and iPSCs, we analyzed the DNA methylation status of a region of the PDGFRB promoter that contains 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 PDGFRB, and identifying sites of active DNA demethylation, is essential for future applications of iPSC-derived fibroblasts for regenerative medicine.
authors.affiliation: Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Hewitt
authors.forename: Yulia
authors.initials: Y
authors.lastname: Shamis
authors.forename: Elana
authors.initials: E
authors.lastname: Knight
authors.forename: Avi
authors.initials: A
authors.lastname: Smith
authors.forename: Anna
authors.initials: A
authors.lastname: Maione
authors.forename: Addy
authors.initials: A
authors.lastname: Alt-Holland
authors.forename: Steven D
authors.initials: SD
authors.lastname: Sheridan
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Haggarty
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Garlick
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000032:analysis / Q000737:chemistry; D019175:DNA Methylation / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*
chemical_list: D004247:DNA; D020797:Receptor, Platelet-Derived Growth Factor beta