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

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  • Irène Aksoy

    (Inserm, U846, 18 Avenue Doyen Lepine
    Stem Cell and Brain Research Institute
    Université de Lyon, Université Lyon 1
    Genome Institute of Singapore, 60 Biopolis street)

  • Vincent Giudice

    (Inserm, U846, 18 Avenue Doyen Lepine
    Stem Cell and Brain Research Institute
    Université de Lyon, Université Lyon 1)

  • Edwige Delahaye

    (Inserm, U846, 18 Avenue Doyen Lepine
    Stem Cell and Brain Research Institute
    Université de Lyon, Université Lyon 1)

  • Florence Wianny

    (Inserm, U846, 18 Avenue Doyen Lepine
    Stem Cell and Brain Research Institute
    Université de Lyon, Université Lyon 1)

  • Maxime Aubry

    (Inserm, U846, 18 Avenue Doyen Lepine
    Stem Cell and Brain Research Institute
    Université de Lyon, Université Lyon 1)

  • Magali Mure

    (Inserm, U846, 18 Avenue Doyen Lepine
    Stem Cell and Brain Research Institute
    Université de Lyon, Université Lyon 1)

  • Jiaxuan Chen

    (Genome Institute of Singapore, 60 Biopolis street)

  • Ralf Jauch

    (Genome Institute of Singapore, 60 Biopolis street
    Genome Regulation Laboratory, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences)

  • 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
    Center for Genomic Regulation (CRG), C. Dr. Aiguader 88
    Universitat Pompeu Fabra (UPF), C. Dr. Aiguader 88)

  • Michael Xavier Doss

    (Universitat Pompeu Fabra (UPF), C. Dr. Aiguader 88
    Present address: Stem Cell Center, Masonic Medical Research Laboratory, Utica, New York-13501, USA)

  • 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
    Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra)

  • Pierre-Yves Bourillot

    (Inserm, U846, 18 Avenue Doyen Lepine
    Stem Cell and Brain Research Institute
    Université de Lyon, Université Lyon 1)

  • Pierre Savatier

    (Inserm, U846, 18 Avenue Doyen Lepine
    Stem Cell and Brain Research Institute
    Université de Lyon, Université Lyon 1)

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.

Suggested Citation

  • 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 &, 2014. "Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells," Nature Communications, Nature, vol. 5(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4719
    DOI: 10.1038/ncomms4719
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    Cited by:

    1. Stephen Huang & Casie Reed & Melissa Ilsley & Graham Magor & Michael Tallack & Michael Landsberg & Helen Mitchell & Kevin Gillinder & Andrew Perkins, 2024. "Mutations in linker-2 of KLF1 impair expression of membrane transporters and cytoskeletal proteins causing hemolysis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. K. A. Gajewska & H. Lescesen & M. Ramialison & K. M. Wagstaff & D. A. Jans, 2021. "Nuclear transporter Importin-13 plays a key role in the oxidative stress transcriptional response," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Hans-Juergen Schulten & Deema Hussein, 2019. "Array expression meta-analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas," PLOS ONE, Public Library of Science, vol. 14(5), pages 1-20, May.

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