Induced expression of Fndc5 significantly increased cardiomyocyte differentiation rate of mouse embryonic stem cells

Gene. 2014 Nov 10;551(2):127-37. doi: 10.1016/j.gene.2014.08.045. Epub 2014 Aug 26.

Abstract

Fibronectin type III domain-containing 5 protein (Fndc5) is an exercise hormone and its transcript profile in mouse showed high degree of expression in heart, skeletal muscle and brain. Our previous studies indicated a significant increase (approximately 10 fold) in mRNA level of Fndc5 when embryonic stem cells were differentiated into beating bodies. As a step closer to identify the involvement of Fndc5 in the process of cardiomyocyte differentiation, we generated a stably inducible transduced mouse embryonic stem cell (mESC) line that overexpressed Fndc5 following Doxycycline induction. Our results indicated that the overexpression of Fndc5 during spontaneous cardiac differentiation significantly increased not only at RNA levels for mesodermal markers but also at the transcriptional levels for cardiac progenitor and cardiac genes. These data suggest that Fndc5 may be involved in cardiomyocyte differentiation. Therefore, a new hope will be arisen for potential application of this myokine for regeneration of damaged cardiac tissues especially in cardiac failure.

Keywords: Cardiac differentiation; Embryonic stem cells; Fndc5; Overexpression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / genetics*
  • Cell Line
  • Doxycycline / pharmacology
  • Embryoid Bodies / metabolism
  • Embryonic Stem Cells / metabolism*
  • Fetal Proteins / genetics
  • Fibronectins / genetics*
  • Fibronectins / metabolism
  • Forkhead Transcription Factors / genetics
  • Gene Expression / drug effects
  • HEK293 Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Mice
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Box Domain Proteins / genetics
  • Time Factors

Substances

  • Dkk1 protein, mouse
  • FNDC5 protein, mouse
  • Fetal Proteins
  • Fibronectins
  • Forkhead Transcription Factors
  • Foxc1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • T-Box Domain Proteins
  • Brachyury protein
  • Doxycycline