Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells

Nat Commun. 2014 Apr 28;5:3719. doi: 10.1038/ncomms4719.


Krüppel-like factors (Klf) 4 and 5 are two closely related members of the Klf family, known to play key roles in cell cycle regulation, somatic cell reprogramming and pluripotency. Here we focus on the functional divergence between Klf4 and Klf5 in the inhibition of mouse embryonic stem (ES) cell differentiation. Using microarrays and chromatin immunoprecipitation coupled to ultra-high-throughput DNA sequencing, we show that Klf4 negatively regulates the expression of endodermal markers in the undifferentiated ES cells, including transcription factors involved in the commitment of pluripotent stem cells to endoderm differentiation. Knockdown of Klf4 enhances differentiation towards visceral and definitive endoderm. In contrast, Klf5 negatively regulates the expression of mesodermal markers, some of which control commitment to the mesoderm lineage, and knockdown of Klf5 specifically enhances differentiation towards mesoderm. We conclude that Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in murine ES cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / physiology*
  • Chromatin Immunoprecipitation
  • Embryonic Stem Cells / physiology*
  • Endoderm / embryology*
  • Flow Cytometry
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Knockdown Techniques
  • High-Throughput Nucleotide Sequencing
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Mesoderm / embryology*
  • Mice
  • Microarray Analysis
  • Real-Time Polymerase Chain Reaction


  • GKLF protein
  • Klf5 protein, mouse
  • Kruppel-Like Transcription Factors

Associated data

  • GEO/GSE49848