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Thrombopoiesis is spatially regulated by the bone marrow vasculature

Author

Listed:
  • David Stegner

    (University Hospital Würzburg)

  • Judith M. M. vanEeuwijk

    (University Hospital Würzburg)

  • Oğuzhan Angay

    (University of Würzburg)

  • Maximilian G. Gorelashvili

    (University Hospital Würzburg)

  • Daniela Semeniak

    (University Hospital Würzburg)

  • Jürgen Pinnecker

    (University of Würzburg)

  • Patrick Schmithausen

    (University of Würzburg)

  • Imke Meyer

    (Charité-University Hospital Berlin)

  • Mike Friedrich

    (University of Würzburg)

  • Sebastian Dütting

    (University Hospital Würzburg)

  • Christian Brede

    (University Hospital Würzburg)

  • Andreas Beilhack

    (University Hospital Würzburg)

  • Harald Schulze

    (University Hospital Würzburg
    Charité-University Hospital Berlin)

  • Bernhard Nieswandt

    (University Hospital Würzburg
    University of Würzburg)

  • Katrin G. Heinze

    (University of Würzburg)

Abstract

In mammals, megakaryocytes (MKs) in the bone marrow (BM) produce blood platelets, required for hemostasis and thrombosis. MKs originate from hematopoietic stem cells and are thought to migrate from an endosteal niche towards the vascular sinusoids during their maturation. Through imaging of MKs in the intact BM, here we show that MKs can be found within the entire BM, without a bias towards bone-distant regions. By combining in vivo two-photon microscopy and in situ light-sheet fluorescence microscopy with computational simulations, we reveal surprisingly slow MK migration, limited intervascular space, and a vessel-biased MK pool. These data challenge the current thrombopoiesis model of MK migration and support a modified model, where MKs at sinusoids are replenished by sinusoidal precursors rather than cells from a distant periostic niche. As MKs do not need to migrate to reach the vessel, therapies to increase MK numbers might be sufficient to raise platelet counts.

Suggested Citation

  • David Stegner & Judith M. M. vanEeuwijk & Oğuzhan Angay & Maximilian G. Gorelashvili & Daniela Semeniak & Jürgen Pinnecker & Patrick Schmithausen & Imke Meyer & Mike Friedrich & Sebastian Dütting & Ch, 2017. "Thrombopoiesis is spatially regulated by the bone marrow vasculature," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00201-7
    DOI: 10.1038/s41467-017-00201-7
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    Cited by:

    1. Till Fabian Mertens & Alina Tabea Liebheit & Johanna Ehl & Ralf Köhler & Asylkhan Rakhymzhan & Andrew Woehler & Lukas Katthän & Gernot Ebel & Wjatscheslaw Liublin & Ana Kasapi & Antigoni Triantafyllop, 2024. "MarShie: a clearing protocol for 3D analysis of single cells throughout the bone marrow at subcellular resolution," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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