Thrombopoiesis is spatially regulated by the bone marrow vasculature

David Stegner (), Judith M. M. vanEeuwijk, Oğuzhan Angay, Maximilian G. Gorelashvili, Daniela Semeniak, Jürgen Pinnecker, Patrick Schmithausen, Imke Meyer, Mike Friedrich, Sebastian Dütting, Christian Brede, Andreas Beilhack, Harald Schulze, Bernhard Nieswandt and Katrin G. Heinze ()
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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
Bernhard Nieswandt: University Hospital Würzburg
Katrin G. Heinze: University of Würzburg

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00201-7

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