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

Irène Aksoy, Vincent Giudice, Edwige Delahaye, Florence Wianny, Maxime Aubry, Magali Mure, Jiaxuan Chen, Ralf Jauch, Gireesh K. Bogu, Tobias Nolden, Heinz Himmelbauer, Michael Xavier Doss, Agapios Sachinidis, Herbert Schulz, Oliver Hummel, Paola Martinelli, Norbert Hübner, Lawrence W. Stanton, Francisco X. Real, Pierre-Yves Bourillot () and Pierre Savatier ()
Additional contact information
Irène Aksoy: Inserm, U846, 18 Avenue Doyen Lepine
Vincent Giudice: Inserm, U846, 18 Avenue Doyen Lepine
Edwige Delahaye: Inserm, U846, 18 Avenue Doyen Lepine
Florence Wianny: Inserm, U846, 18 Avenue Doyen Lepine
Maxime Aubry: Inserm, U846, 18 Avenue Doyen Lepine
Magali Mure: Inserm, U846, 18 Avenue Doyen Lepine
Jiaxuan Chen: Genome Institute of Singapore, 60 Biopolis street
Ralf Jauch: Genome Institute of Singapore, 60 Biopolis street
Gireesh K. Bogu: Genome Institute of Singapore, 60 Biopolis street
Tobias Nolden: Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73
Heinz Himmelbauer: Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73
Michael Xavier Doss: Universitat Pompeu Fabra (UPF), C. Dr. Aiguader 88
Agapios Sachinidis: Center of Physiology and Pathophysiology, Institute of Neurophysiology, Robert-Koch-Strasse. 39
Herbert Schulz: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10
Oliver Hummel: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10
Paola Martinelli: Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3
Norbert Hübner: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10
Lawrence W. Stanton: Genome Institute of Singapore, 60 Biopolis street
Francisco X. Real: Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3
Pierre-Yves Bourillot: Inserm, U846, 18 Avenue Doyen Lepine
Pierre Savatier: Inserm, U846, 18 Avenue Doyen Lepine

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms4719

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