Scientists from the University of Würzburg successfully elucidated new details about a circuit regulating platelet biogenesis. These important findings could contribute to a better understanding of the mechanism leading to bleeding disorders.
Platelets play a crucial role in hemostasis. At sites of vascular damage they attach to the subendothelial matrix, form a plug that seals the wound and contribute to tissue repair. Due to their short lifespan, new platelets need to be constantly generated.
Confocal microscope image of intact murine bone marrow. The mature megakaryocyte (green) attaches to blood vessel (red) and releases new platelets into the blood stream. Cell nuclei are shown in blue.
Photo: AG Nieswandt
To this end, giant precursor cells in the bone marrow, so-called megakaryocytes, undergo a complex maturation process and finally release platelets into the bloodstream. Defects in platelet biogenesis can result in dramatically decreased numbers or malfunctioning of circulating platelets, thus affecting hemostasis in patients. Unfortunately, the detailed mechanisms regulating megakaryocyte maturation and platelet biogenesis still remain elusive.
Modifications cause drastic consequences
Researchers from the Rudolf Virchow Center for Experimental Biomedicine and the University Hospital Würzburg now succeeded in identifying a decisive regulatory circuit in platelet biogenesis. The group of Prof. Bernhard Nieswandt was able to decipher vital regulating factors in megakaryocytes.
Small proteins, the Rho-GTPases, serve as molecular switches in the regulation of important cellular functions such as maturation, as well as orientation towards the blood vessels. Thus, the RHo-GTPases allow megakaryocytes to properly produce platelets.
´We could show that the complete absence or even a defect of these switches disrupts the orientation of the megakaryocyte, which then transmigrate through the blood vessel.´ says Prof. Nieswandt, director of the study. Indeed, under these conditions normal platelet biogenesis is abolished, leading to a drastic decrease in platelet count and bleeding complications in mice.
These astonishing findings built the basis for a new understanding of platelet generation in bone marrow and most likely also provide new insights into the development of other blood cells.
Therapeutical approach in bleeding disorders
The discovery of this Rho-GTPase-dependent regulatory circuit in platelet biogenesis encourages the scientists to gain new insights in bleeding disorders, such as the Bernard-Soulier Syndrome. Patients suffering from this disorder endure a severe reduction of the platelet count, which is accompanied by a life-long profound bleeding complication.
´Our results open the way for new therapeutic approaches to treat diseases which are connected to defective platelet biogenesis.´ hopes Prof. Nieswandt.
The scientists recently published their new findings together with other international researchers in the journal Nature Communications.
Dütting, S. et al. (2017). A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis. Nature Communications. 8, 15838 doi: 10.1038/ncomms15838.
Prof. Dr. Bernhard Nieswandt (Chair Experimental Biomedicine – Vascular Medicine, Rudolf-Virchow-Center)
Tel. +49 (0)9 31/ 31 - 80405, firstname.lastname@example.org
Katja Aurbach (PhD student, Dept. Experimental Biomedicine - Vascular Medicine)
+49 (0)9 31/ 31 - 99813, aurbach_K1@ukw.de
Dr. Frank Sommerlandt (Public Science Center, Rudolf-Virchow-Center)
Tel. 0931 31 88449, email@example.com
Dr. Frank Sommerlandt | idw - Informationsdienst Wissenschaft
Fish recognize their prey by electric colors
13.11.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
The dawn of a new era for genebanks - molecular characterisation of an entire genebank collection
13.11.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly
The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
13.11.2018 | Life Sciences
13.11.2018 | Life Sciences
13.11.2018 | Awards Funding