Activin A supplement in the hESCs culture enhances the endoderm differentiation efficiency

Cell Biol Int. 2014 Jul;38(7):849-56. doi: 10.1002/cbin.10274. Epub 2014 Mar 25.

Abstract

Activin A is a critical regulator in human embryonic stem cells (hESCs) maintenance and differentiation. Different concentrations of Activin A affect hESC maintenance and differentiation in different ways. A high concentration favors anterior primitive streak and gives rise to DE if the stimulation persists. hESCs were cultured with and without 10 ng/mL Activin A supplement respectively. The two groups of cells were differentiated into endoderm cells with 100 ng/mL Activin A and other reagents. Microarray-based DNA methylation was analyzed with the Infinium Human Methylation450 BeadChip on these two groups. There was a significant difference in endoderm differentiation efficiency (average efficiency: 71 vs. 58.5%, P < 0.05). hESCs cultured with Activin A supplement had an increased propensity to form definitive endoderm cells in response to Activin A and Wnt signal. Differentially Methylated Regions (DMRs) between these two groups were found. DMRs were related to the stem cell maintenance and gene regulation by peroxisome proliferators via PPARα, indicating that hESCs maintained with Activin A supplement had stronger "stemness."

Keywords: Activin A; differentiately methylated regions; differentiation; human embryonic stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / pharmacology*
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • CpG Islands
  • DNA Methylation
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects*
  • Endoderm / cytology*
  • Endoderm / metabolism
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • PPAR alpha / metabolism
  • Wnt Signaling Pathway / drug effects

Substances

  • PPAR alpha
  • activin A
  • Activins