SDF-1-enhanced cardiogenesis requires CXCR4 induction in pluripotent stem cells

Anca Chiriac, Andre Terzic, Sungjo Park, Yasuhiro Ikeda, Randolph Faustino, Timothy J. Nelson

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Transformation of pluripotent stem cells into cardiac tissue is the hallmark of cardiogenesis, yet procardiogenic signals remain partially understood. Preceding cardiogenic induction, a surge in CXCR4 chemokine receptor expression in the early stages of stem cell lineage specification coincides with the acquisition of pre-cardiac profiles. Accordingly, CXCR4 selection, in conjunction with mesoderm-specific VEGF type II receptor FLK-1 co-expression, segregates cardiogenic populations. To assess the functionality of the CXCR4 biomarker, targeted activation and disruption were here exploited in the context of embryonic stem cell-derived cardiogenesis. Implicated as a cardiogenic hub through unbiased bioinformatics analysis, induction of the CXCR4/SDF-1 receptor- ligand axis triggered enhanced beating activity in stem cell progeny. Gene expression knockdown of CXCR4 disrupted spontaneous embryoid body differentiation and blunted the expression of cardiogenic markers MEF2C, Nkx2.5, MLC2a, MLC2v, and cardiac-MHC. Exogenous SDF-1 treatment failed to rescue cardiogenic-deficient phenotype, demonstrating a requirement for CXCR4 expression in mediating SDF-1 effects. Thus, a pro-cardiogenic signaling role for the CXCR4/SDF1 axis is herein revealed within pluripotent stem cell progenitors, exposing a functional target to promote lineage-specific differentiation.

Original languageEnglish (US)
Pages (from-to)674-682
Number of pages9
JournalJournal of cardiovascular translational research
Volume3
Issue number6
DOIs
StatePublished - Dec 2010

Keywords

  • CXCR4
  • Cardiogenesis
  • Pluripotent stem cells
  • SDF-1

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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