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, Jonathan A. Garlick

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Platelet-derived growth factor receptor-beta (PDGFRb) 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 PDGFRb 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.

Original languageEnglish (US)
Pages (from-to)2276-2287
Number of pages12
JournalJournal of cell science
Volume125
Issue number9
DOIs
StatePublished - May 1 2012

Keywords

  • 3D tissues
  • DNA methylation
  • Fibroblasts
  • Human embryonic stem cells
  • Induced pluripotent stem cells
  • PDGFRβ

ASJC Scopus subject areas

  • Cell Biology

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