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Emergency program ensures blood coagulation

No. 37c4 | 21/08/2015

During infections, the body frequently suffers severe loss of platelets, or thrombocytes. This can result in serious health problems such as hemorrhage and even septic shock. Until now, it has not been known how the body rapidly furnishes the necessary quantity of thrombocytes to promote coagulation following their stress-related loss.

In bone sections a strong increase in the number of polyploid megakaryocytes (red cells) was observed after treatment of mice with IFN

Scientists in the team of Marieke Essers and her doctoral student Simon Haas have now discovered an emergency program in mice that bypasses the known pathway of blood stem cell differentiation so that the vital thrombocytes are rapidly replenished. Dr. Essers is a research scientist at HI-STEM, the stem cell institute jointly sponsored by the German Cancer Research Center and the Dietmar Hopp Foundation.

Essers and her co-workers have discovered, within the hematopoietic stem cells, a small cell population that is defined molecularly to induce differentiation of megakaryocytes, the progenitors of platelets. This population of quiescent stem cells does not provide the normal supply of platelets but serves as an emergency backup.

When quiescent, these cells express only few proteins. In the event of an acute infection, they are aroused from their quiescent state by the messenger substance interferon α, express the typical megakaryocyte proteins and are rapidly differentiated into advanced precursor cells. This emergency system rapidly replaces the thrombocytes that were lost as a result of the infection.

This elegant emergency backup bypasses the lengthy process of normal hematopoietic cell differentiation, thereby ensuring that any life-threatening loss of thrombocytes is compensated for quickly. However, repeated infections can result in the reservoir of emergency stem cells being depleted.

Simon Haas, Jenny Hansson, Daniel Klimmeck, Dirk Loeffler, Lars Velten, Hannah Uckelmann, Stephan Wurzer, Áine M. Prendergast, Alexandra Schnell, Klaus Hexel, Rachel Santarella-Mellwig, Sandra Blaszkiewicz, Andrea Kuck, Hartmut Geiger, Michael D. Milsom, Lars M. Steinmetz, Timm Schroeder, Andreas Trumpp, Jeroen Krijgsveld, Marieke A. G. Essers: Inflammation-induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors. Cell Stem Cell 2015, 10.1016/j.stem.2014.07.005

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Cancer Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.


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