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Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells

Author

Listed:
  • Céline Souilhol

    (Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter)

  • Christèle Gonneau

    (Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter)

  • Javier G. Lendinez

    (Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter)

  • Antoniana Batsivari

    (Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter)

  • Stanislav Rybtsov

    (Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter)

  • Heather Wilson

    (Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter)

  • Lucia Morgado-Palacin

    (Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter)

  • David Hills

    (Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter)

  • Samir Taoudi

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research)

  • Jennifer Antonchuk

    (STEMCELL Technologies Inc., Vancouver)

  • Suling Zhao

    (Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter)

  • Alexander Medvinsky

    (Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter)

Abstract

During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta–gonad–mesonephros (AGM) region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso–ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs.

Suggested Citation

  • Céline Souilhol & Christèle Gonneau & Javier G. Lendinez & Antoniana Batsivari & Stanislav Rybtsov & Heather Wilson & Lucia Morgado-Palacin & David Hills & Samir Taoudi & Jennifer Antonchuk & Suling Z, 2016. "Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10784
    DOI: 10.1038/ncomms10784
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    Cited by:

    1. Brandon Hadland & Barbara Varnum-Finney & Stacey Dozono & Tessa Dignum & Cynthia Nourigat-McKay & Adam M. Heck & Takashi Ishida & Dana L. Jackson & Tomer Itkin & Jason M. Butler & Shahin Rafii & Cole , 2022. "Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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