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Zeb1-Hdac2-eNOS circuitry identifies early cardiovascular precursors in naive mouse embryonic stem cells

Author

Listed:
  • Chiara Cencioni

    (Goethe University
    Institute of Cell Biology and Neurobiology (IBCN))

  • Francesco Spallotta

    (Goethe University)

  • Matteo Savoia

    (Goethe University
    Università Cattolica di Roma)

  • Carsten Kuenne

    (Max Planck Institute for Heart and Lung Research)

  • Stefan Guenther

    (Max Planck Institute for Heart and Lung Research)

  • Agnese Re

    (Institute of Cell Biology and Neurobiology (IBCN))

  • Susanne Wingert

    (Goethe University)

  • Maike Rehage

    (Goethe University)

  • Duran Sürün

    (Goethe University)

  • Mauro Siragusa

    (Goethe University)

  • Jacob G. Smith

    (University College London)

  • Frank Schnütgen

    (Goethe University)

  • Harald von Melchner

    (Goethe University)

  • Michael A. Rieger

    (Goethe University)

  • Fabio Martelli

    (IRCCS-Policlinico San Donato)

  • Antonella Riccio

    (University College London)

  • Ingrid Fleming

    (Goethe University)

  • Thomas Braun

    (Max-Planck-Institute for Heart and Lung Research)

  • Andreas M. Zeiher

    (Goethe University)

  • Antonella Farsetti

    (Institute of Cell Biology and Neurobiology (IBCN)
    Goethe University)

  • Carlo Gaetano

    (Goethe University
    Istituti Clinici Scientifici Maugeri)

Abstract

Nitric oxide (NO) synthesis is a late event during differentiation of mouse embryonic stem cells (mESC) and occurs after release from serum and leukemia inhibitory factor (LIF). Here we show that after release from pluripotency, a subpopulation of mESC, kept in the naive state by 2i/LIF, expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes NO. This eNOS/NO-positive subpopulation (ESNO+) expresses mesendodermal markers and is more efficient in the generation of cardiovascular precursors than eNOS/NO-negative cells. Mechanistically, production of endogenous NO triggers rapid Hdac2 S-nitrosylation, which reduces association of Hdac2 with the transcriptional repression factor Zeb1, allowing mesendodermal gene expression. In conclusion, our results suggest that the interaction between Zeb1, Hdac2, and eNOS is required for early mesendodermal differentiation of naive mESC.

Suggested Citation

  • Chiara Cencioni & Francesco Spallotta & Matteo Savoia & Carsten Kuenne & Stefan Guenther & Agnese Re & Susanne Wingert & Maike Rehage & Duran Sürün & Mauro Siragusa & Jacob G. Smith & Frank Schnütgen , 2018. "Zeb1-Hdac2-eNOS circuitry identifies early cardiovascular precursors in naive mouse embryonic stem cells," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03668-0
    DOI: 10.1038/s41467-018-03668-0
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