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Science 21 September 2007:
Vol. 317. no. 5845, pp. 1767 - 1770
DOI: 10.1126/science.1146304
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Reports

Dynamic Visualization of Thrombopoiesis Within Bone Marrow

Tobias Junt,1 Harald Schulze,2* Zhao Chen,2 Steffen Massberg,1 Tobias Goerge,1 Andreas Krueger,2{dagger} Denisa D. Wagner,1 Thomas Graf,4 Joseph E. Italiano, Jr.,3 Ramesh A. Shivdasani,2{ddagger} Ulrich H. von Andrian1{ddagger}

Platelets are generated from megakaryocytes (MKs) in mammalian bone marrow (BM) by mechanisms that remain poorly understood. Here we describe the use of multiphoton intravital microscopy in intact BM to visualize platelet generation in mice. MKs were observed as sessile cells that extended dynamic proplatelet-like protrusions into microvessels. These intravascular extensions appeared to be sheared from their transendothelial stems by flowing blood, resulting in the appearance of proplatelets in peripheral blood. In vitro, proplatelet production from differentiating MKs was enhanced by fluid shear. These results confirm the concept of proplatelet formation in vivo and are consistent with the possibility that blood flow–induced hydrodynamic shear stress is a biophysical determinant of thrombopoiesis.

1 Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
2 Dana-Farber Cancer Institute, Boston, MA 02115, USA.
3 Hematology Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
4 Centre de Regulacio Genomica, Parc de Recesca Biomedica de Barcelona, 08003 Barcelona, Spain.

* Present address: Klinik für Allgemeine Pädiatrie, Charite, Labor für Pädiatrische Molekularbiologie, 10117 Berlin, Germany.

{dagger} Present address: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.

{ddagger} To whom correspondence should be addressed. E-mail: uva{at}hms.harvard.edu (U.H.v.A.); ramesh_shivdasani{at}dfci.harvard.edu (R.A.S.)

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