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Inhibition of endothelial ERK signalling by Smad1/5 is essential for haematopoietic stem cell emergence

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Listed:
  • Chunxia Zhang

    (State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences)

  • Junhua Lv

    (State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences)

  • Qiuping He

    (State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences)

  • Sifeng Wang

    (State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences)

  • Ya Gao

    (State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences)

  • Anming Meng

    (State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Xiao Yang

    (State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology)

  • Feng Liu

    (State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences)

Abstract

The earliest HSCs are derived from haemogenic endothelium via endothelial-to-haematopoietic transition during vertebrate embryogenesis; however, the underlying mechanism is largely unclear. Here we show that interplay of Smad1/5 and ERK signalling is essential for haemogenic endothelium-based HSC emergence. Smad1/5 directly inhibits erk expression through recruiting HDAC1 to and inducing de-acetylation of the erk promoter in endothelial cells. Over-activated ERK signalling conferred by inhibition of Smad1/5 promotes the arterial endothelial cell fate and constitutively strengthens the tight junction between endothelial cells, thereby repressing the specification of haemogenic endothelium and the following endothelial-to-haematopoietic transition process. These findings provide new insights into the in vitro generation of transplantable HSCs for potential clinical applications.

Suggested Citation

  • Chunxia Zhang & Junhua Lv & Qiuping He & Sifeng Wang & Ya Gao & Anming Meng & Xiao Yang & Feng Liu, 2014. "Inhibition of endothelial ERK signalling by Smad1/5 is essential for haematopoietic stem cell emergence," Nature Communications, Nature, vol. 5(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4431
    DOI: 10.1038/ncomms4431
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