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The expression of Sox17 identifies and regulates haemogenic endothelium

Nature Cell Biology volume 15, pages 502510 (2013) | Download Citation

Abstract

Although it is well recognized that haematopoietic stem cells (HSCs) develop from a specialized population of endothelial cells known as haemogenic endothelium, the regulatory pathways that control this transition are not well defined. Here we identify Sox17 as a key regulator of haemogenic endothelial development. Analysis of Sox17–GFP reporter mice revealed that Sox17 is expressed in haemogenic endothelium and emerging HSCs and that it is required for HSC development. Using the mouse embryonic stem cell differentiation model, we show that Sox17 is also expressed in haemogenic endothelium generated in vitro and that it plays a pivotal role in the development and/or expansion of haemogenic endothelium through the Notch signalling pathway. Taken together, these findings position Sox17 as a key regulator of haemogenic endothelial and haematopoietic development.

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Acknowledgements

We thank S. Morrison and H. Lickert for sharing of mice and mESC lines. We thank C. Sturgeon, A. Ditadi and B. Chanda for advice and technical support with the studies and comments on the manuscript. This work was supported by the Canadian Institutes of Health Research (CIHR MOP-95369) and the National Institutes of Health (NIH 5U01 HL100395)

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Affiliations

  1. McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario M5G 1L7, Canada

    • Raedun L. Clarke
    •  & Gordon Keller
  2. The Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA

    • Amanda D. Yzaguirre
    • , Yumi Yashiro-Ohtani
    • , Warren S. Pear
    •  & Nancy A. Speck
  3. Université Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium

    • Antoine Bondue
    •  & Cedric Blanpain

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Contributions

R.C. and G.K. designed experiments and wrote the manuscript. G.K. supervised the project. R.C. performed all mESC and transplantation experiments. A.Y. performed confocal imaging. Y.Y. performed JASPER analysis and luciferase assays. A.B. and C.B. generated the doxycycline-inducible mESC line.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Gordon Keller.

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DOI

https://doi.org/10.1038/ncb2724

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